Terminology Criteria For Adverse Events Research Articles

A dosiomics model for prediction of radiation-induced acute skin toxicity in breast cancer patients: machine learning-based study for a closed bore linac

BackgroundRadiation induced acute skin toxicity (AST) is considered as a common side effect of breast radiation therapy. The goal of this study was to design dosiomics-based machine learning (ML) models for prediction of AST, to enable creating optimized treatment plans for high-risk individuals.MethodsDosiomics features extracted using Pyradiomics tool (v3.0.1), along with treatment plan-derived dose volume histograms (DVHs), and patient-specific treatment-related (PTR) data of breast cancer patients were used for modeling. Clinical scoring was done using the Common Terminology Criteria for Adverse Events (CTCAE) V4.0 criteria for skin-specific symptoms. The 52 breast cancer patients were grouped into AST 2 + (CTCAE ≥ 2) and AST 2 − (CTCAE < 2) toxicity grades to facilitate AST modeling. They were randomly divided into training (70%) and testing (30%) cohorts. Multiple prediction models were assessed through multivariate analysis, incorporating different combinations of feature groups (dosiomics, DVH, and PTR) individually and collectively. In total, seven unique combinations, along with seven classification algorithms, were considered after feature selection. The performance of each model was evaluated on the test group using the area under the receiver operating characteristic curve (AUC) and f1-score. Accuracy, precision, and recall of each model were also studied. Statistical analysis involved features differences between AST 2 − and AST 2 + groups and cutoff value calculations.ResultsResults showed that 44% of the patients developed AST 2 + after Tomotherapy. The dosiomics (DOS) model, developed using dosiomics features, exhibited a noteworthy improvement in AUC (up to 0.78), when spatial information is preserved in the dose distribution, compared to DVH features (up to 0.71). Furthermore, a baseline ML model created using only PTR features for comparison with DOS models showed the significance of dosiomics in early AST prediction. By employing the Extra Tree (ET) classifiers, the DOS + DVH + PTR model achieved a statistically significant improved performance in terms of AUC (0.83; 95% CI 0.71–0.90), accuracy (0.70), precision (0.74) and sensitivity (0.72) compared to other models.ConclusionsThis study confirmed the benefit of dosiomics-based ML in the prediction of AST. However, the combination of dosiomics, DVH, and PTR yields significant improvement in AST prediction. The results of this study provide the opportunity for timely interventions to prevent the occurrence of radiation induced AST.

Multilevel Characteristics of Cumulative Symptom Burden in Young Survivors of Childhood Cancer

Symptom burden and its characteristics among survivors of pediatric cancers aged 8 to 18 years remain understudied. To examine the prevalence of symptom burden among young childhood cancer survivors and identify associations with sociodemographic, clinical, and psychological resilience skills, and health-related quality of life (HRQOL). A cross-sectional analysis using data collected from November 1, 2017, to January 31, 2019, in a survivorship clinic at a US-based comprehensive cancer center was conducted. Participants included 302 dyads of children aged 8 to 18 years who survived at least 5 years beyond diagnosis and their primary caregivers. Data analysis was performed from March 13, 2023, to February 29, 2024. Diagnosis, caregiver-reported family conflict, self-reported caregiver anxiety, neighborhood-level social vulnerability, and survivor-reported meaning and purpose. Novel symptom-level burden, integrating the attributes of severity and daily activity interference using the pediatric version of the Patient-Reported Outcomes Version of the Common Terminology Criteria for Adverse Events, global cumulative symptom burden, and HRQOL using the EuroQol-5D. Multinomial logistic regression identified characteristics associated with symptom burden; linear regression assessed symptom burden and HRQOL associations. Among 302 survivors (mean [SD] age, 14.2 [2.9] years, mean [SD] time since diagnosis, 10.9 [2.9] years; 153 [50.7%] male), 186 (62.0%) had low, 77 (25.7%) moderate, and 37 (12.3%) high global cumulative symptom burden. Greater caregiver anxiety was associated with moderate (risk ratio [RR], 1.56; 95% CI, 1.09-2.24) global symptom burden. Greater neighborhood deprivation was associated with moderate global symptom burden (RR, 4.86; 95% CI, 1.29-18.26). Survivors with greater meaning/purpose were less likely to have moderate (RR, 0.42; 95% CI, 0.29-0.61) and high (RR, 0.27; 95% CI, 0.16-0.46) global symptom burden. The burden of individual symptoms displayed similar patterns. Low (Cohen d, -0.60; 95% CI, -0.87 to -0.32) and moderate/high (d, -0.98; 95% CI, -1.53 to -0.43) general pain, moderate/high numbness (d, -0.99; 95% CI, -1.69 to -0.29), and moderate/high worry (d, -0.55; 95% CI, -0.99 to -0.11) were associated with lower HRQOL. In this cross-sectional study of young childhood cancer survivors, symptom burden was prevalent. Caregiver anxiety and disparity-related neighborhood factors were associated with greater symptom burden, whereas meaning and purpose was a protective factor. Greater specific symptom burden contributed to poorer HRQOL. The findings suggest that interventions targeting resilience and neighborhood adversity may alleviate symptom burden and improve HRQOL.

Preliminary efficacy and safety of YSCH-01 in patients with advanced solid tumors: an investigator-initiated trial

ObjectiveTo evaluate the safety and preliminary efficacy of YSCH-01 (Recombinant L-IFN adenovirus) in subjects with advanced solid tumors.MethodsIn this single-center, open-label, investigator-initiated trial of YSCH-01, 14 patients with advanced solid...

Mining Real-World Big Data to Characterize Adverse Drug Reaction Quantitatively: Mixed Methods Study.

Adverse drug reactions (ADRs), which are the phenotypic manifestations of clinical drug toxicity in humans, are a major concern in precision clinical medicine. A comprehensive evaluation of ADRs is helpful for unbiased supervision of marketed drugs and for discovering new drugs with high success rates. In current practice, drug safety evaluation is often oversimplified to the occurrence or nonoccurrence of ADRs. Given the limitations of current qualitative methods, there is an urgent need for a quantitative evaluation model to improve pharmacovigilance and the accurate assessment of drug safety. In this study, we developed a mathematical model, namely the Adverse Drug Reaction Classification System (ADReCS) severity-grading model, for the quantitative characterization of ADR severity, a crucial feature for evaluating the impact of ADRs on human health. The model was constructed by mining millions of real-world historical adverse drug event reports. A new parameter called Severity_score was introduced to measure the severity of ADRs, and upper and lower score boundaries were determined for 5 severity grades. The ADReCS severity-grading model exhibited excellent consistency (99.22%) with the expert-grading system, the Common Terminology Criteria for Adverse Events. Hence, we graded the severity of 6277 standard ADRs for 129,407 drug-ADR pairs. Moreover, we calculated the occurrence rates of 6272 distinct ADRs for 127,763 drug-ADR pairs in large patient populations by mining real-world medication prescriptions. With the quantitative features, we demonstrated example applications in systematically elucidating ADR mechanisms and thereby discovered a list of drugs with improper dosages. In summary, this study represents the first comprehensive determination of both ADR severity grades and ADR frequencies. This endeavor establishes a strong foundation for future artificial intelligence applications in discovering new drugs with high efficacy and low toxicity. It also heralds a paradigm shift in clinical toxicity research, moving from qualitative description to quantitative evaluation.

Efficacy of Episil® in patients with hematologic malignancies: a comparative study

BackgroundEpisil® is a nonabsorbable liquid medical material used to coat and protect the mucosa in patients with oral mucositis. A few studies have reported its efficacy in patients with head and neck cancer. However, reports on its use in patients with hematologic malignancies are scarce. Thus, we aimed to evaluate the efficacy of Episil for the treatment of oral mucositis in patients with acute myelogenous leukemia, malignant lymphoma, acute lymphocytic leukemia, multiple myeloma, and myelodysplastic syndrome.MethodsBetween May 2018 and March 2019, a total of thirty-seven patients with acute myelogenous leukemia, malignant lymphoma, acute lymphocytic leukemia, multiple myeloma, and myelodysplastic syndrome who received Episil® for the treatment of oral mucositis were included in this study. All patients were treated at the Hiroshima Red Cross and Atomic-bomb Surgery Hospital. To determine the severity of oral mucositis, 22 out of the 37 patients were interviewed and compared objectively using the Common Terminology Criteria for Adverse Events, version 3.0. In addition, subjective measures of the effects of oral mucositis were assessed using an original evaluation protocol (a unique evaluation chart specific to the Department of Oral Surgery, Hiroshima Red Cross & Atomic-bomb Survivors Hospital).ResultsOut of 37 participants recruited in the study, 31 (84%) described the sensation of Episil® as very good or good. Moreover, the severity of mucositis was found to decrease after the use of Episil® in seven patients out of 22 (19%), particularly in those with mucositis at multiple sites. Participants' evaluations revealed pain relief and improvement in speech and feeding functions. Participants with grade 3 mucositis reported a greater improvement in pain relief, speech, and feeding functions than those with grade 2 mucositis.ConclusionsThis study suggests the efficacy of Episil® in treating oral mucositis in patients with hematologic malignancies, particularly in those with oral mucositis at multiple sites. In addition to pain relief, Episil® may improve speech and feeding functions.

Sequential administration of peripheral nerve blocks andonabotulinumtoxinA for the treatment of chronic migraine andother headache disorders-A retrospective tolerability and safety study.

To determine the tolerability and safety of concurrent peripheral nerve blocks and onabotulinumtoxinA treatment during a single outpatient clinic procedure visit. Procedural interventions are available for the treatment of headache disorders. OnabotulinumtoxinA and peripheral nerve blocks are used as alternatives or in addition to oral therapies to reduce the frequency and intensity of migraine attacks. There is currently a lack of safety data focusing on the sequential administration of local anesthetic via peripheral nerve blocks and onabotulinumtoxinA during a single clinical encounter for the treatment of headache. The primary aim of the study was to determine the safety and tolerability of concurrent peripheral nerve blockade and onabotulinumtoxinA injections during a single outpatient clinic procedure visit. We hypothesized that the dual intervention would be safe and well tolerated by patients with chronic migraine and other headache disorders. A retrospective chart review was performed using clinical data from patients seen by multiple providers over a 16-month timeframe at one outpatient headache clinic. Patients were identified by procedure codes and those receiving peripheral nerve block(s) and onabotulinumtoxinA injections during a single encounter within the study period were eligible for inclusion. Inclusion criteria were (1) patients 18 years and older who were (2) receiving both peripheral nerve blocks and onabotulinumtoxinA injections for the treatment of chronic migraine. Patients were excluded if they were under age 18, received their procedure outside of the clinic (emergency room, inpatient ward), or were receiving sphenopalatine ganglion blocks. Age- and sex-matched patients who received one procedure, either peripheral nerve blocks or onabotulinumtoxinA, were used for control. The primary outcome of this safety study was the number of adverse events that occurred in the dual intervention group compared to the single intervention control arms. Information regarding adverse events was gathered via retrospective chart review. If an adverse event was recorded, it was then graded by the reviewer utilizing the Common Terminology Criteria for Adverse Events ranging from Grade 1 Mild Event to Grade 5 Death. Additionally, it was noted whether the adverse event led to treatment discontinuation. In total, 375 patients were considered eligible for inclusion in the study. After age and sex matching of controls, 131 patients receiving dual intervention were able to be compared to 131 patients receiving onabotulinumtoxinA alone and 104 patients receiving dual intervention were able to be compared to 104 patients receiving peripheral nerve block(s) alone. The primary endpoint analysis showed no significant difference in total adverse events between dual intervention compared to nerve blocks alone or onabotulinumtoxinA alone. The number of adverse events that led to treatment discontinuation approached but did not reach statistical significance for those receiving dual intervention versus onabotulinumtoxinA alone in the number of adverse events that led to treatment termination (4.6%, 6/131 vs. 0.8%, 1/131, p = 0.065); however, the number of patients who discontinued therapy was not significantly different between those groups (2.3%, 3/131 vs. 0.8%, 1/131; p = 0.314; odds ratio 0.3 [0-3.2]; p = 0.338). In this retrospective chart review, there was no significant difference in adverse events or therapy discontinuation between patients receiving sequential peripheral nerve block(s) and onabotulinumtoxinA injections versus those receiving either peripheral nerve block(s) or onabotulinumtoxinA injections alone. As a result, we concluded that the combination procedure is likely safe and well tolerated in routine clinical practice.

Daratumumab and antineoplastic therapy versus antineoplastic therapy only for adults with newly diagnosed multiple myeloma ineligible for transplant.

Multiple myeloma (MM) is a haematological malignancy that is characterised by proliferation of malignant plasma cells in the bone marrow. For adults ineligible to receive high-dose chemotherapy and autologous stem cell transplant, the recommended treatment combinations in first-line therapy generally consist of combinations of alkylating agents, immunomodulatory drugs, and proteasome inhibitors. Daratumumab is a CD38-targeting, human IgG1k monoclonal antibody recently developed and approved for the treatment of people diagnosed with MM. Multiple myeloma cells uniformly over-express CD-38, a 46-kDa type II transmembrane glycoprotein, making myeloma cells a specific target for daratumumab. To determine the benefits and harms of daratumumab in addition to antineoplastic therapy compared to antineoplastic therapy only for adults with newly diagnosed MM who are ineligible for transplant. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, EU Clinical Trials Register, ClinicalTrials.gov, WHO ICTRP, and conference proceedings from 2010 to September 2023. We included randomised controlled trials that compared treatment with daratumumab added to antineoplastic therapy versus the same antineoplastic therapy alone in adult participants with a confirmed diagnosis of MM. We excluded quasi-randomised trials and trials with less than 80% adult participants, unless there were subgroup analyses of adults with MM. Two review authors independently screened the results of the search strategies for eligibility. We documented the process of study selection in a flowchart as recommended by the PRISMA statement. We evaluated the risk of bias in included studies with RoB 1 and assessed the certainty of the evidence using GRADE. We followed standard Cochrane methodological procedures. We included four open-label, two-armed randomised controlled trials (34 publications) involving a total of 1783 participants. The ALCYONE, MAIA, and OCTANS trials were multicentre trials conducted worldwide in middle- and high-income countries. The AMaRC 03-16 trial was conducted in one high-income country, Australia. The mean age of participants was 69 to 74 years, and the proportion of female participants was between 40% and 54%. All trials evaluated antineoplastic therapies with or without daratumumab. In the ALCYONE and OCTANS trials, daratumumab was combined with bortezomib and melphalan-prednisone. In the AMaRC 03-16 study, it was combined with bortezomib, cyclophosphamide, and dexamethasone, and in the MAIA study, it was combined with lenalidomide and dexamethasone. None of the included studies was blinded (high risk of performance and detection bias). One study was published as abstract only, therefore the risk of bias for most criteria was unclear. The other three studies were published as full texts. Apart from blinding, the risk of bias was low for these studies. Overall survival Treatment with daratumumab probably increases overall survival when compared to the same treatment without daratumumab (hazard ratio (HR) 0.64, 95% confidence interval (CI) 0.53 to 0.76, 2 studies, 1443 participants, moderate-certainty evidence). After a follow-up period of 36 months, 695 per 1000 participants survived in the control group, whereas 792 per 1000 participants survived in the daratumumab group (95% CI 758 to 825). Progression-free survival Treatment with daratumumab probably increases progression-free survival when compared to treatment without daratumumab (HR 0.48, 95% CI 0.39 to 0.58, 3 studies, 1663 participants, moderate-certainty evidence). After a follow-up period of 24 months, progression-free survival was reached in 494 per 1000 participants in the control group versus 713 per 1000 participants in the daratumumab group (95% CI 664 to 760). Quality of life Treatment with daratumumab may result in a very small increase in quality of life after 12 months, evaluated on the EORTC QLQ-C30 global health status scale (GHS), when compared to treatment without daratumumab (mean difference 2.19, 95% CI -0.13 to 4.51, 3 studies, 1096 participants, low-certainty evidence). The scale is from 0 to 100, with a higher value indicating a better quality of life. On-study mortality Treatment with daratumumab probably decreases on-study mortality when compared to treatment without daratumumab (risk ratio (RR) 0.72, 95% CI 0.62 to 0.83, 3 studies, 1644 participants, moderate-certainty evidence). After the longest follow-up available (12 to 72 months), 366 per 1000 participants in the control group and 264 per 1000 participants in the daratumumab group died (95% CI 227 to 304). Serious adverse events Treatment with daratumumab probably increases serious adverse events when compared to treatment without daratumumab (RR 1.18, 95% CI 1.02 to 1.37, 3 studies, 1644 participants, moderate-certainty evidence). After the longest follow-up available (12 to 72 months), 505 per 1000 participants in the control group versus 596 per 1000 participants in the daratumumab group experienced serious adverse events (95% CI 515 to 692). Adverse events (Common Terminology Criteria for Adverse Events (CTCAE) grade ≥ 3) Treatment with daratumumab probably results in little to no difference in adverse events (CTCAE grade ≥ 3) when compared to treatment without daratumumab (RR 1.01, 95% CI 0.99 to 1.02, 3 studies, 1644 participants, moderate-certainty evidence). After the longest follow-up available (12 to 72 months), 953 per 1000 participants in the control group versus 963 per 1000 participants in the daratumumab group experienced adverse events (CTCAE grade ≥ 3) (95% CI 943 to 972). Treatment with daratumumab probably increases the risk of infections (CTCAE grade ≥ 3) when compared to treatment without daratumumab (RR 1.52, 95% CI 1.30 to 1.78, 3 studies, 1644 participants, moderate-certainty evidence). After the longest follow-up available (12 to 72 months), 224 per 1000 participants in the control group versus 340 per 1000 participants in the daratumumab group experienced infections (CTCAE grade ≥ 3) (95% CI 291 to 399). Overall analysis of four studies showed a potential benefit for daratumumab in terms of overall survival and progression-free survival and a slight potential benefit in quality of life. Participants treated with daratumumab probably experience increased serious adverse events. There were likely no differences between groups in adverse events (CTCAE grade ≥ 3); however, there are probably more infections (CTCAE grade ≥ 3) in participants treated with daratumumab. We identified six ongoing studies which might strengthen the certainty of evidence in a future update of this review.

Abstract PO1-28-08: The Efficacy and Safety Results of Neoadjuvant Phase II study of Anlotinib plus Sintilimab Combined with Chemotherapy in Triple-negative Breast Cancer (NeoSACT)

Abstract Background: In triple-negative breast cancer (TNBC), the co-administration of programmed mortality 1 (PD-1) inhibitors and chemotherapy has demonstrated enhanced pathological complete response (pCR) rates and improved event-free survival (EFS). Previous research has suggested that antiangiogenic agents possess the ability to normalize aberrant tumor vasculature, thereby converting the immune-suppressive tumor microenvironment into an immune-supportive one. This study aims to assess the effectiveness and safety of combining the neoadjuvant small-molecule antiangiogenic drug Antilotinib with the PD-1 inhibitor Sintilimab and chemotherapy. Methods: In this study, a single-arm, open-label, phase II trial was conducted to evaluate the effectiveness of Anlotinib plus Sintilimab, in conjunction with nab-paclitaxel and carboplatin, followed by epirubicin and cyclophosphamide, in eligible patients with stage II-III TNBC. The treatment regimen consisted of four cycles of nab-paclitaxel (100 mg/m² on day 1, 8 and 15) plus carboplatin (AUC 5) every 21 days, followed by four cycles of epirubicin (90 mg/m2) plus cyclophosphamide (600 mg/m2) every 21 days. Additionally, patients received Sintilimab (200mg) every 21 days and Antilotinib (12mg, po on day 1-14, every 21 days) for eight cycles. Patient enrollment was conducted according to a Simon two-stage design. The primary endpoint was the rate of pCR based on the definition of ypT0/Tis ypN0. Secondary endpoints included residual cancer burden (RCB), EFS, overall survival (OS), adverse events (AE), and immune response biomarkers. Results: Between September 2021 and August 2023, a cohort of 31 patients was enrolled, with a median age of 48 years (range: 30-70 years). Among the participants, 21 out of 31 (67.8%) presented with clinical stage II disease, 23 out of 31 (74.2%) had T2 tumors, and 19 out of 31 (61.3%) exhibited clinically positive lymph nodes. In the initial phase of the study, a total of 11 patients were evaluated, out of which 7 patients achieved a pathological complete response (pCR) after surgery. Consequently, 20 patients were included in the subsequent stage, and among the 19 patients who were evaluable, 13 achieved pCR. One participant withdrew from the study prematurely following the third cycle due to grade 3 liver impairment, resulting in the discontinuation of study therapy as well as subsequent surgery. In the intention-to-treat (ITT) population, the overall pCR rate was determined to be 64.5% (20/31, 95% CI 45.4% - 80.8%). Additionally, 80.6% (25/31, 95%CI 62.5% - 92.5%) of the patients were assessed as having a RCB score of 0 or 1. A total of 31 patients were subjected to adverse event assessment. Among them, 12 patients (38.7%) experienced one or more grade 3/4 adverse events (AEs) according to the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. The grade 3/4 AEs encompassed rash (7 patients, 22.6%), anemia (4 patients, 12.9%), thrombocytopenia (3 patients, 9.7%), neutropenia (2 patients, 6.4%), leukopenia (2 patients, 6.4%), hypothyroidism (2 patients, 6.4%), and elevated AST/ALT (1 patient, 3.2%). Conclusions: The neoadjuvant regimen comprising the combination of Anlotinib and Sintilimab alongside chemotherapy demonstrated a pCR rate of 64.5%, with no observed emergence of novel toxicity signals. Ongoing investigations encompass biomarker assessments and survival analyses. Pertinent clinical trial details can be found under the identifier NCT04877821. Citation Format: Liulu Zhang, Mei Yang, Ciqiu Yang, Teng Zhu, Hong-Fei Gao, Kun Wang. The Efficacy and Safety Results of Neoadjuvant Phase II study of Anlotinib plus Sintilimab Combined with Chemotherapy in Triple-negative Breast Cancer (NeoSACT) [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-28-08.

Abstract PO3-17-12: Safety and efficacy of Atezolizumab in combination with nab-Paclitaxel in patients with PD-L1 positive metastatic or locally advanced triple-negative breast cancer: A pan-UK cancer centre experience

Abstract BACKGROUND Within the United Kingdom (UK), combination chemo-immunotherapy with Atezolizumab and nab-Paclitaxel is National Institute for Health and Care Excellence (NICE) approved as a first line palliative systemic treatment option for patients with advanced triple-negative breast cancer (aTNBC) with programmed death-ligand 1 (PD-L1) expression ≥1%. Trials demonstrated progression-free survival (PFS) and overall survival (OS) benefits. Treatment-related toxicities may impact on quality of life and result in treatment delay or discontinuation. We conducted a National Service Evaluation (SE) to assess the safety and efficacy in a “real-world” dataset. METHODS Data from patients with aTNBC who received Atezolizumab/nab-Paclitaxel between 9th March 2019 and 2022 across 10 UK Cancer Centres were analysed. All grade 1-4 toxicities were recorded in accordance with Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 scoring system. Participation was contingent on local approval for this project, and data transferred following receipt of a data sharing agreement. Kaplan-Meier curves for PFS and OS were calculated. RESULTS 129 patients were included in the analysis with a median age of 55 (30-82). 42.6% (n=55) had a PS of 0, 51.2% (n=66) a PS of 1 and 3.9% (n=5) had a PS of 2. Atezolizumab/nab-Paclitaxel was given in the first line setting in most patients (84.5%, n= 109), but in 15.5% (n=20) in the second line setting (privately insured). 21.7% (n=28) of patients presented with de novo metastatic disease, 58.1% (n=75) of patients were post-menopausal and 6.2% (n=8) had a BRCA1 or 2 mutation. 76.7% of patients (n=99) had previous neo-/adjuvant treatment in the non-metastatic setting: 55.8% had prior treatment with a taxane, 51.2% anthracycline, 22.5% platinum, and 66.7% had prior radiotherapy. 83.7% (n= 108) had invasive ductal breast cancer, and 84.5% (n=109) presented with 0-3 number of metastatic sites with 15.5% (n=20) having ≥ 4 metastatic sites. Here, the nodal metastatic site dominated in 78.3% of patients. Grade ≥ 3 events occurred in 21.7% (n=28) of patients. These were decreased neutrophil count (10.1%, n=13), pyrexia (2.3%, n=3), diarrhoea (1.6%, n=2), hypothyroidism (1.6%, n=2), peripheral neuropathy (1.6%, n=2), anaemia (1.6%, n=2), GGT rise (0.8%, n=1), fatigue (0.8%, n=1), hypophysitis (0.8%, n=1), pneumonitis (0.8%, n=1), nausea (0.8%, n=1), mucositis (0.8%, n=1), platelet count decreased (0.8%, n=1), infections (0.8%, n=1). Increased rates of Grade ≥ 3 colitis (2.3%, n=3) and hepatitis (3%, n=2.3) were observed. 20.2% (n=26) of patients required steroids to treat toxicities. Reason for treatment discontinuation included in 58.1% (n=75) disease progression, and 7.8% (n=10) unacceptable toxicity. In 22.5% of patients’ treatment was still ongoing at time of data lock. At approximately 12 weeks, 7.8% of patients had a complete and 51.2% a partial response, 10.1% had stable and 22.5% progressive disease and for 8.5% the response was not known as they have not yet reached 12 weeks since treatment start. Median PFS was 5 months and OS was 14 months. CONCLUSIONS The toxicity profile of Atezolizumab/nab-Paclitaxel was comparable to literature, however, both PFS and OS were shorter. In comparison to the IMpassion130 trial data, patients within this national SE project were less fit and more heavily pre-treated. A higher number of any grade hyperthyroidism and fatigue, and of grade ≥ 3 colitis and hepatitis were noticed. Baseline patient characteristics XX- XX Citation Format: Jasmin V Waterhouse, Alexandra Holdich, Florentia Mina, Mariam Obeid, Kroopa Joshi, Sophie Barrett, Lavarniya Rajakumar, Gemma McCormick, Sally Seymour, Panagiotis Koliou, Rushan Sylva, Olubukola Ayodele, Ashram Gautam, Jenny Smith, Jenny McKeon, Thomas Strawson-Smith, Rosalie Douglas, Annabel Borley, Apostolos Konstantis, Sophie McGrath. Safety and efficacy of Atezolizumab in combination with nab-Paclitaxel in patients with PD-L1 positive metastatic or locally advanced triple-negative breast cancer: A pan-UK cancer centre experience [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-17-12.

Abstract PO1-22-03: Radiation Toxicity and Treatment Outcomes in Breast Cancer Patients with ATM Pathogenic and VUS Mutations: Implications for Personalized Therapy

Abstract Introduction: Previous studies have shown that ATM (ataxia-telangiectasia mutated) mutations may be associated with increased radiation sensitivity and altered treatment response. However, there is a limited understanding of the clinical implications and optimal management strategies for breast cancer patients with ATM mutations receiving radiotherapy (RT). The aim of our study is to assess the impact of ATM mutations on radiation response and treatment outcomes in breast cancer patients undergoing RT. Material and Methods: A total of 79 female patients diagnosed with breast cancer were included in the study, with 31 (39.3%) having pathogenic (P) and likely pathogenic (LP) variants (all of the variants were heterozygous) and 48 (60.8%) having VUS variants detected through whole ATM gene sequencing screening for patients in accordance with NCCN clinical practice guideline. Statistical analysis, including descriptive, graphical, and inferential methods, such as the Kolmogorov-Smirnov test, Mann-Whitney U Test, and Chi-square tests, was conducted using SPSS version 25.0 to evaluate the normal distribution of continuous variable scores and perform quantitative and qualitative comparisons between groups at a 95% confidence level (p &amp;lt; 0.05). Results: The median age of the patients was 44 years (range: 24-74), with 75% of them being 50 years old or younger .The rate of breast cancer in patients with VUS variants was significantly higher in those aged 50 and below compared to those with P/LP variants (83% vs. 61%, p=0.028). There was no statistically significant difference in clinical stage, tumour histological type, and molecular subtype classification based on ATM gene variant type (P/LP vs. VUS) among the patients (p&amp;gt;0.05), but the rate of high tumour grade was significantly higher in the VUS variant group (65% vs. 40%, p=0.034). The rate of patients who received RT was 87%, with 26 patients receiving radiation to the breast or chest wall and 43 patients receiving additional regional lymph node irradiation. There were no statistically significant differences in surgical and systemic treatment types and RT dose based on ATM gene variant type (P/LP vs. VUS) (p&amp;gt;0.05). Among the patients who received RT, 33 (48%) experienced early-stage skin reactions, and 15 (22%) experienced late-stage skin reactions according to Common Terminology Criteria for Adverse Events (CTCAE) v5. No Grade 3, 4 and 5 early and late toxicity were observed . The rate of early (83% vs. 23%; p&amp;lt; 0.001) and late (35% vs. 13%; p=0.029) skin reactions was significantly higher in the P/LP variant group compared to the VUS variant group. Grade I lymphedema was observed in 2 (2.5%) patients, 1 (3.2%) in the P/LP group and 1 (2.1%) in the VUS group (p&amp;gt;0.05). Among the 23 patients who underwent breast reconstruction, 1 (4%) had implant revision and 1 (4%) experienced implant loss, both of which were observed in the pathogenic variant group (p&amp;gt;0.05). Conclusion: Limited clinical data exists on RT toxicity in breast cancer patients with ATM gene mutations, and clear guidelines for decision-making are lacking. Our study revealed higher rates of acute and chronic skin reactions in the P/LP variant group, highlighting the need for further investigation into the impact of these variants on treatment outcomes and patient management. However, it is crucial to manage these reactions effectively and not allow them to hinder treatment. Additional research and interventions are warranted to better understand and address these reactions, aiming to enhance the overall treatment experience and outcomes for patients with ATM gene mutations. Citation Format: Evrim Tezcanli, Seda Eroz, Ugur Ozbek, Ahmet Yesilyurt, CIHAN URAS, Nuran Bese. Radiation Toxicity and Treatment Outcomes in Breast Cancer Patients with ATM Pathogenic and VUS Mutations: Implications for Personalized Therapy [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-22-03.

Abstract PO1-20-03: Acupuncture for Preventing Progression of Taxane-Induced PeripheralNeuropathy (ATP): A Phase II Randomized, Placebo Controlled Trial

Abstract Background: Chemotherapy-induced peripheral neuropathy (CIPN) from chemotherapy drugs such as taxanes can be detrimental to cancer survival, increasing the risk of falls and worsening physical functions. However, there is no effective treatment or preventative measure for CIPN. The current management of worsening and persistent CIPN during chemotherapy is dose reduction or discontinuation of chemotherapy. Our group previously completed a single-arm phase IIA pilot trial of women who developed National Cancer Institution Common Terminology Criteria for Adverse Events (NCI-CTCAE) grade 2 CIPN during weekly paclitaxel for stage I-III breast cancer. The result suggested an acupuncture intervention for grade 2 CIPN might slow CIPN progression during chemotherapy. However, the role of acupuncture still needs to be better defined. Trial design: The ATP trial is a two-arm, parallel, randomized controlled trial comparing weekly real acupuncture (RA) versus sham acupuncture (SA) during preplanned curative intent taxane containing regimens in patients with breast cancer. The study will include two phases: screening and intervention. In the screening phase, eligible patients will consent and receive CIPN screening each week. Patients who develop grade 1 CIPN or higher based on NCI-CTCAE version 5.0 will be consented to the intervention phase and randomized to receive either weekly RA or SA using a standardized, semi-fixed protocol developed in our preliminary studies to improve CIPN pain. Eligibility criteria for the screening phase: English or Spanish-proficient; aged ≥18 years; histological diagnoses of invasive carcinoma of the breast; and plan to receive curative intent chemotherapy regimen containing paclitaxel or nab-paclitaxel weekly or biweekly as standard of care. Eligibility criteria for the intervention phase: in additional to the screening phase eligibility criteria, developed CIPN grade ≥1 based on the NCI-CTCAE version 5.0, while receiving taxane; ≥ four weeks of paclitaxel or nab-paclitaxel weekly or biweekly planned, as standard of care and at treating physician’s discretion; willing to adhere to requirement that no new pain medication or dose changes be taken throughout the first 12 weeks of the study period; and willing to adhere to all study-related procedures, including randomization to one of the two possible acupuncture treatments. Specific aims: The primary aim is to evaluate the effectiveness of RA versus SA in preventing taxane-induced peripheral neuropathy progression as measured by Neuropathic Pain Scale (NPS) in patients with early-stage breast cancer who are receiving curative intent neurotoxic chemotherapy. The secondary aim is to evaluate the effectiveness of RA versus SA on chemotherapy relative dose intensity (RDI) and CIPN-related chemotherapy discontinuation. Statistical methods: We will randomize 80 patients, 40 to each arm. All randomized patients will be evaluable in the Intent to Treat (ITT) analyses because all will have completed the baseline assessment before randomization. We will use a linear mixed model (LMM) to compare the change in NPS between the arms from baseline to week 4. Based on our pilot data, a difference in CIPN grade from 1 to 2 corresponded to a difference in NPS from 12 to 22, a difference of ten points in 27 patients. The NPS standard deviation (SD) in patients with grade 1 CIPN was 17. With 80 patients we will have 80% power to detect a difference between arms as small as 10 points on the NPS, assuming a one-sided test, type I error of 5%, correlation between baseline and follow-up measurements of 0.5, SD of 17, and 15% attrition at week 4. Present accrual and target accrual: We accrued 20 participants in the intervention phase by the end of June 2023; the target accrual is 80 participants. Contact information for people with a specific interest in the trial: W. Iris Zhi, MD, PhD, zhiw@mskcc.org. ClinicalTrails.gov Identifier: NCT05458284. Citation Format: W. Iris Zhi, Lauren Taylor, Raymond Baser, Matthew Weitzman, Qing Li, Christina Seluzicki, Ting Bao, Jun Mao. Acupuncture for Preventing Progression of Taxane-Induced PeripheralNeuropathy (ATP): A Phase II Randomized, Placebo Controlled Trial [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-20-03.

Abstract PO2-22-03: Reirradiation for locally recurrent breast cancer: a long-term single centre experience

Abstract Background: About 10–15% of patients with breast cancer will eventually develop an ipsilateral breast recurrence. The management of cancer relapse in previously irradiated tissues is a challenging therapeutic issue, and data on breast re-irradiation are currently lacking. Hence, the aim of this work was to report our experience with breast re-irradiation for non-metastatic recurrent breast cancer. Material and Methods: All patients who underwent a breast or chest wall re-irradiation in the Institut Curie, Paris, France between 2003 and 2019 were identified. Those who underwent re-irradiation only in other volumes than the ipsilateral breast were excluded. Local recurrence-free (LRFS), overall survival (OS), disease-specific survival (DSS), progression-free survival (PFS), and metastasis-free survival (MFS) were evaluated. Physician-reported acute and late toxicities were assessed using the Common Terminology Criteria for Adverse Events (CTCAE) 5.0. Results: Between 2003 and 2019, 21.372 patients underwent a breast irradiation in our institution. Of these, 453 received a new irradiation to the controlateral breast and/or lymph nodes, 105 to the homolateral lymph nodes without breast/chest wall re-irradiation and 28 received a second course of radiotherapy (RT) to the homolateral breast. These 28 patients were included in this study. Median follow up after re-irradiation was 45.5 months (IQR 33.5-79.75 months). The median age at the time of second breast RT was 63 years (IQR, 49-78). The median RT dose to the breast/chest wall was 60 Gy (interquartile range (IQR) 50-66 Gy) for the first irradiation and 48 Gy (IQR 30-50 Gy) for the second. The median cumulative dose was 100 Gy (IQR 92-114 Gy). The median time between the two courses of RT was 47 months (IQR 22.75-109.5 months). Eighteen (64%) patients were treated with a curative intent and 10 (36%) for palliative purposes. Ten (36%) had a macroscopic breast residue at re-irradiation. The second RT course was performed with electrons, photons and a combination of both in 13 (46%), 8 (29%) and 6 (21%) patients, respectively. At 2 years, LRFS, OS, DSS, PFS and MFS were respectively 59%, 79%, 82%, 50% and 75% in the whole cohort. 2-year-LRFS (72% vs 31%, p=0.02), OS (94% vs 50%, p&amp;lt; 0.01), DSS (94% vs 56%, p&amp;lt; 0.01) and PFS (61% vs 20%, p=0.02) differed significantly between patients treated in a curative or in a palliative intent, but not MFS (78% vs 69%, p=0.77). Among patients, 8 (29%) remained relapse-free 5 years after the second course of RT. Only one patient experienced an acute grade 3 adverse event (dermatitis), and 1 presented a late grade 3 one (skin fibrosis). One patient with major cardiovascular risk factors died of myocardial infarction 13 months after the second left breast irradiation. Conclusion: Breast or chest wall re-irradiation appears to be feasible with good disease control in patients treated with a curative intent, and acceptable toxicity rates. In addition, a significant number of patients were disease-free 5 years after the second course of RT. Prospective larger data with longer follow-up are needed to confirm these findings. Citation Format: Jérémy Baude, Rémi Dendale, Alain Fourquet, Youlia Kirova. Reirradiation for locally recurrent breast cancer: a long-term single centre experience [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-22-03.

Abstract PO4-18-07: A dose escalation and cohort expansion study of the CDK9 inhibitor KB-0742 in triple negative breast cancer and transcriptionally addicted relapsed or refractory solid tumors

Abstract Background: MYC deregulation is a hallmark of triple negative breast cancer (TNBC) and is associated with aggressive tumors and poor clinical outcomes. Although MYC remains undrugged, targeting of its cofactors has emerged as an attractive strategy to inhibit MYC oncogenic activity. Cyclin-dependent kinase 9 (CDK9) is a critical regulator of oncogenic MYC expression and an important MYC cofactor. KB-0742 is an oral CDK9 inhibitor that demonstrates promising preclinical activity against TNBC. In a real-world cohort, TNBCs have higher MYC expression and higher rates of MYC genomic amplification than other breast cancer subtypes. In primary patient-derived cell lines, KB-0742 treatment results in stronger cytotoxic effects in TNBC as compared to other subtypes. In patient-derived organoids and patient-derived xenografts, CDK9 inhibition by KB-0742 drives antiproliferative and anti-tumor growth effects, including in models that are resistant to standard of care. KB-0742 strongly downregulates MYC protein levels at doses that only partially inhibit CDK9 activity, suggesting a therapeutic window for tumor-specific activity (Saffran, D.C. et al, 2021). KB-0742 is currently being evaluated in a phase 1/2 dose escalation and cohort expansion study in patients with TNBC and other transcriptionally addicted tumors (NCT04718675). Trial design: This phase 1/2 study includes two parts: dose escalation (part 1) and cohort expansion (part 2). Part 2 includes cohort A (solid tumors with high prevalence of MYC overexpression including TNBC, non-small cell lung cancer and ovarian) and cohort B (other transcriptionally addicted tumor types including sarcomas, adenoid cystic carcinoma, nut midline carcinoma and small cell lung cancer). KB-0742 is dosed orally once daily for 3 consecutive days, followed by 4 days, off on a weekly basis in 28-day cycles until unacceptable toxicity or disease progression. Eligibility criteria: Part 1 dose escalation is open to patients with relapsed or refractory solid tumors. Part 2 is defined by tumor indications in cohorts A and B. Eligibly criteria include age &amp;gt; 18 years (≥ 12 years old and with a body weight ≥ 40 kg part 2 for cohort B), acceptable organ function, and ECOG PS &amp;lt; 2. Specific aims: Primary objectives include evaluation of pharmacokinetics (PK), pharmacodynamics (PD), safety, tolerability, preliminary anti-tumor activity, and identifying a maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D). PK measurements include Cmax, tmax, AUC0-last, accumulation ratio (Racc) and t1/2. Safety data will be evaluated per the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) v5.0. The Modified Continuous Reassessment Method (mCRM) (Goodman et al., Stat Med 1995) will guide dose escalation and MTD. RP2D nomination is informed by PD in peripheral blood mononuclear cells using assays to evaluate phosphorylation of the CDK9 substrate serine 2 on the RNA Polymerase II C-terminal domain (pSER2) and CDK9-responsive gene expression. Radiographic tumor response to KB-0742 in patients is assessed every other cycle starting from cycle two after treatment using RECIST 1.1 criteria. Target accrual: Targeted total enrollment is 170 patients. For additional information, contact clinicaltrials@kronosbio.com Citation Format: Monica Mita, Alain Mita, Miguel Villalona-Calero, Noah Federman, Drew Rasco, David Spigel, Jia Luo, Gregory Cote, Richard Cutler, Pavan Kumar, Crystal MacKenzie, Charles Lin, Jorge DiMartino, Elizabeth Olek, Brian Van Tine. A dose escalation and cohort expansion study of the CDK9 inhibitor KB-0742 in triple negative breast cancer and transcriptionally addicted relapsed or refractory solid tumors [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-18-07.

Abstract PO3-10-10: Are we adequately integrating patient reported outcomes in breast cancer clinical trials?

Abstract Background: Integrating patient reported outcomes (PROs) in cancer care enhances clinical outcomes and creates a paradigm shift in providing patient-centered care. Several studies performed in the past 15 years have demonstrated that systematic monitoring of patients using PROs through surveys improve patient-clinician communication, clinician awareness of symptoms, symptom management, patient satisfaction, quality of life, and overall survival. There has been uncertainty over the type of PRO system to implement in cancer care, how to evaluate PRO in clinical trials, and how to compare this to the clinician common terminology criteria for adverse events (CTCAE). The PRO concept was first introduced in 1975 with the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life (QoL) survey. In May 2018, the National Cancer Institute established the PRO-CTCAE to be utilized for cancer patients to report and grade their treatment related adverse events, like that of clinician reported CTCAE. The goal of our study was to evaluate frequency of PRO incorporation in phase III breast cancer clinical trials. Methods: New England Journal of Medicine, Journal of Clinical Oncology, and Lancet were systematically searched to identify phase III breast cancer clinical trials published between January 2018 and June 2023. A total of 113 phase III studies were identified, 87 of which had reported protocols. Studies that did not demonstrate protocols on these search engines were not included in the review. Of these 87 clinical trials, 36 studies documented evaluation of PRO. These studies were segregated by year of publication. For each year, the number of total phase III breast cancer clinical trials that were published were compared to those that were published and evaluated PRO. A percentage was generated and allowed for a longitudinal trend to be analyzed over a 5-year period to assess if there was improved frequency of PRO integration into breast cancer clinical trials. Summary statistics were calculated using SAS 9.4. Results: 36 of 113 trials demonstrated PRO use and 26 utilized EORTC-QoL, 1 used PRO-CTCAE, and 9 used another measure of PRO assessment within their study protocol (such as FACT-B and PHQ-9. Additionally, in 2018, 33% of published breast cancer studies included PRO data. Since then, there have been fluctuations in breast cancer studies collecting PRO; 2019: 33%, 2020: 47%, 2021: 43%, 2022: 73%, and since the start of 2023: 9%. Conclusions: Our data suggests a trend towards improvement in frequency of PRO data collection in breast cancer clinical trials over the past 5 years, exemplified by the marked increase in 2022. There remains a need to incorporate PROs in clinical trials and routine care to improve patient experience and provide patient-centered care. Citation Format: Yadav Rina, Zhengyan Huang, Jessica Moss, Garima Gupta. Are we adequately integrating patient reported outcomes in breast cancer clinical trials? [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-10-10.

Abstract PS05-01: Accuracy and safety of fibroblast activation protein inhibitor (FAPI) PET/CT in diagnosis of axillary lymph node metastasis in early breast cancer patients: a prospective cohort study (PFB-01&amp;02 study)

Abstract Background Axillary lymph node (ALN) is the most common metastatic site of breast cancer (BC) and the status of ALN determines the staging, treatment and prognosis for BC patients. Traditional imaging techniques, including ultrasound (US), mammography, MRI, and 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) were still unsatisfactory to evaluate the status of ALN non-invasively. Fibroblast activation protein (FAP) is highly expressed in cancer-associated fibroblasts and FAP inhibitor (FAPI) PET has been found quite promising in BC. Well-designed prospective large cohort study concerning the diagnostic performance and safety profile of FAPI PET/CT in detection of ALN metastasis of BC is still lacking. Furthermore, FAPI could be radio-labeled with different radio-nuclides including 68Ga and 18F, and there is yet no data concerning the 18F-labeled FAPI in BC. In this study, we investigated the accuracy of FAPI (both 68Ga-FAPI-04 and Al18F-FAPI-04) PET/CT in newly diagnosed BC patients for assessing ALN metastasis. We also compared the diagnostic performance of FAPI PET/CT with that of 18F-FDG PET/CT and US. Methods This prospective study was approved by the Peking Union Medical College Hospital Ethics Committee and was registered online at NIH ClinicalTrials.gov (NCT05574907, NCT05574920). The inclusion criteria were as follows: (1) age 18-80 years old; (2) newly diagnosed BC confirmed by biopsy or with BI-RADS category 4C or 5 lesions by US. The exclusion criteria were as follows: (1) pregnancy or lactation; (2) patients unwilling to undergo PET/CT scans. All patients received biopsy or surgery on breast lesion and ALN. Patients received FAPI and 18F-FDG PET/CT after enrollment. The safety profile of FAPI PET was monitored after injection using the Common Terminology Criteria for Adverse Events. Two experienced nuclear medicine physicians, who were blinded to the pathological diagnosis and other imaging results, assessed the PET/CT images. It was defined as visually positive if the radioactive uptake of the ALN was higher than that of the adjacent normal tissue. The sensitivity, specificity, accuracy, positive predictive value (PPV), and negative predictive value (NPV) were calculated for each diagnostic test. The McNemar test was applied to compare the differences of sensitivity and specificity between FAPI PET/CT, 18F-FDG PET/CT, and US. All statistical tests were performed two-sided, and P&amp;lt; 0.05 was considered statistically significant. Results In total, 113 patients (27-79 years old, median age 66) were enrolled. 53 patients underwent 68Ga-FAPI-04 PET/CT, and the other 60 patients underwent Al18F-FAPI-04 PET/CT. All patients underwent 18F-FDG PET/CT and US. A total of 53/113 (46.9%) patients were finally diagnosed with ALN metastasis. The sensitivity, specificity, accuracy, PPV, and NPV were 90.6%, 90.0%, 90.3%, 88.9%, and 91.5% for FAPI PET/CT, 84.9%, 73.3%, 78.8%, 73.8%, and 84.6% for 18F-FDG PET/CT, 83.0%, 76.7%, 79.6%, 75.9%, and 83.6% for US, respectively (Table 1). The specificity of FAPI PET/CT was significantly higher than that of 18F-FDG PET/CT (P &amp;lt; 0.05) and US (P &amp;lt; 0.05). The sensitivity of FAPI PET/CT was higher than that of 18F-FDG PET/CT (P= 0.45) and US (P= 0.29). There was no significant difference of sensitivity and specificity between 18F-FDG PET/CT and US (P &amp;gt; 0.05). The sensitivity, specificity, accuracy, PPV, and NPV were 92.0%, 92.9%, 92.5%, 92.0%, and 92.9% for 68Ga-FAPI-04 PET/CT, and 89.3%, 87.5%, 88.3%, 86.2%, and 90.3% for Al18F-FAPI-04 PET/CT, respectively (Table 2). The 68Ga-FAPI-04 PET/CT and Al18F-FAPI-04 PET/CT procedures were well tolerated in all patients. The only adverse event was injection pain in 12/53 (22.6%) patients injected with 68Ga-FAPI-04, and 7/69 (10.1%) patients injected with Al18F-FAPI-04, which might relate to the ethanol in the imaging agent. Conclusion The FAPI PET/CT outperformed 18F-FDG PET/CT and US in the diagnosis of ALN metastasis among early breast cancer patients. The 68Ga-FAPI-04 and Al18F-FAPI-04 PET/CT have similar diagnostic performance. The FAPI PET/CT procedures were well tolerated in all patients. Table 1 Diagnostic performance of FAPI PET/CT, 18F-FDG PET/CT, and ultrasound in the diagnosis of ALN metastasis Table 2 Diagnostic performance of 68Ga-FAPI-04 and Al18F-FAPI-04 PET/CT in diagnosis of ALN metastasis Citation Format: Bo Pan, Zhixin Hao, Chao Ren, Lifan Zhang, Yidong Zhou, Qiang Sun, Li Huo. Accuracy and safety of fibroblast activation protein inhibitor (FAPI) PET/CT in diagnosis of axillary lymph node metastasis in early breast cancer patients: a prospective cohort study (PFB-01&amp;02 study) [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PS05-01.

Abstract PO3-28-04: Ganglioside-Monosialic Acid for Prevention of Peripheral Neuropathy Induced by nab-Paclitaxel in Breast Cancer Patients (HELEN-004): A Randomized, Double-Blind, Phase II Trial

Abstract Introduction Chemotherapy-induced peripheral neuropathy (CIPN) is a dose limiting adverse effect of nab-paclitaxel. Ganglioside-Monosialic Acid (GM1) is an abundant glycosphingolipid in neuronal membranes and studies have shown its potential in preventing CIPN as a neuroprotective factor. This study was conducted to evaluate the effect of GM1 in preventing CIPN induced by nab-paclitaxel in breast cancer patients. Methods This study was a randomized, double-blind, placebo-controlled phase II trial conducted at three hospitals in China (NCT04222790). Female patients 18 to 75 years with early-stage breast cancer who were scheduled to receive nab-paclitaxel containing chemotherapy were randomly assigned to receive GM1 or placebo. Nab- paclitaxel was given 125-150 mg/m2 once per week for 12 cycles or 260 mg/m2 once every 3 weeks for four cycles. GM1 or placebo started one day before chemotherapy and was given once per day for 3 days (day −1, day 1, and day 2). The primary outcome was peripheral neuropathy evaluated by the Functional Assessment of Cancer Treatment Neurotoxicity (FACT-Ntx) subscale at 2 weeks after four cycles of chemotherapy. Other endpoints included peripheral neuropathy evaluated by CTCAE version 4.0, Functional Assessment of Cancer Therapy – General (FACT-G) scores and Functional Assessment of Cancer Therapy – Taxane (FACT-Taxane) scores at 2 weeks after four cycles of chemotherapy. Adverse events were evaluated by CTCAE version 4.0. Additional long-term assessments were performed at 3 months, 6 months, and 1 year after the completion of chemotherapy. All assessments were performed by trained physicians. Results 159 patients were enrolled from April 2020 to June 2021, with 79 patients assigned to the GM1 group and 80 patients to the placebo group. Eight patients in the GM1 group and eight patients in the placebo group did not complete the endpoint assessments. In total, 71 patients in GM1 group and 72 in placebo group were evaluated. Baseline characteristics were generally well balanced between groups. After four cycles of Nab-paclitaxel containing chemotherapy, Patients in the GM1 group reported similar mean FACT-Ntx subscale 36.1 (35.1-37.0) with patients in the placebo group 36.4 (35.3-37.3). Compared with baseline, the mean FACT-Ntx score at two weeks after four cycles of chemotherapy decreased by 7.9 in the GM1 group (p&amp;lt; 0.001) and 7.6 in the placebo group (p&amp;lt; 0.001). The difference between GM1 group and placebo group was not statistically significant (P=0.703). No difference was observed in secondary outcomes except that GM1 group showed lower FACT G scores (61.0, 95% CI, 58.1-63.9) than the control group (67.0, 95% CI, 63.2-70.8) at two weeks after four cycles of chemotherapy, the difference was statistically significant (P=0.014). The main results of primary and secondary outcomes were summarized in Table 1. Random assignment was stratified by age (&amp;lt; 60 or &amp;gt;=60) and BMI ((&amp;lt; 24 or &amp;gt;=24). Subgroup analysis was performed for patients in different age and BMI groups. Overall, patients above 60 years old showed lower FACT-Ntx score at than patients under 60 (34.1 and 36.5, respectively. P=0.056). Overweight patients (BMI &amp;gt;=24) showed similar FACT-Ntx score with patients with BMI smaller than 24 (36.8 and 35.7, respectively. P=0.095). The FACT-Ntx score was not significantly different between the GM1 and placebo group in different age and BMI subgroups. The most common adverse events, including myalgia-arthralgia, nausea, vomit, and diarrhea, were evaluated according to CTCAE version 4.0. Incidence and severity of adverse events were not statistically significantly different between the two groups. Conclusion GM1 did not prevent peripheral neuropathy induced by nab-paclitaxel in breast cancer patients. The effect of GM1 in preventing CIPN is still inconclusive and further studies are needed. Caution in recommending GM1 to prevent CIPN is clearly warranted. Table 1. FACT-Ntx subscale, CTCAE version 4.0, FACT-Taxane and FACT G at 2 weeks after four cycles chemotherapy. a. FACT-Ntx: Functional Assessment of Cancer Treatment- Neurotoxicity; b. CTCAE4.0: Common Terminology Criteria for Adverse Events; c. FACT-Taxane: Functional Assessment of Cancer Treatment – Taxane; d. FACT G: Functional Assessment of Cancer Treatment- General. Citation Format: Zhenduo Lu, Dechuang Jiao, Jianghua Qiao, Hao Zhang, Hao Dai, Xianfu Sun, Min Yan, Yong Zhou, Lianfang Li, Chengzheng Wang, Xiuchun Chen, Zhenzhen Liu. Ganglioside-Monosialic Acid for Prevention of Peripheral Neuropathy Induced by nab-Paclitaxel in Breast Cancer Patients (HELEN-004): A Randomized, Double-Blind, Phase II Trial [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-28-04.

Abstract PO2-17-12: Phase I Trial of alpha-lactalbumin vaccine in high risk operable triple negative breast cancer (TNBC) and patients at high genetic risk for TNBC

Abstract Background: Triple-negative breast cancer (TNBC) has a poor prognosis and may be associated with germline mutations. α-Lactalbumin (aLA) is expressed in lactating breasts but not at other times or in other tissues. Expression of aLA is found in 70% of TNBC (PMID: 27322324) so could be an immunologic target for TNBC based on the “retired protein hypothesis” (PMID: 31926646). In pre-clinical studies, vaccination with aLA provided protection from development of autochthonous tumors in transgenic murine models of breast cancer and inhibited growth of established 4T1 transplantable breast tumors in BALB/c mice (PMID: 20512124). Methods: To determine the safety and immunogenicity of aLA, patients with early stage TNBC are being entered in a Phase I trial of aLA with GMP-grade zymosan adjuvant in Montanide ISA 51 VG vehicle. Subjects receive 3 vaccinations given once every 2 weeks. Events of Common Terminology Criteria for Adverse Events (CTCAE) grade ≥ 2 are considered dose-limiting toxicities (DLTs). Results: CTCAE toxicity by dose level is summarized below. All DLTs were injection site reactions, with ulceration and need for incisional drainage representing the grade 3 events. Seven (7) of 10 patients assayed to date have met protocol specified definitions of an immune response based on ELISpot assays to determine frequencies of T cells producing IFNγ and IL-17 in response to recombinant aLA. Assays for an additional 6 patients will be available in September 2023. Conclusion: Dose level ≤ 2 appears to be the maximum tolerated dose. Based on immune response, additional intermediate dose levels may be studied. An additional cohort of patients receiving concurrent anti-PD1 treatment is being accrued. Accrual of patients with BRCA1/2 or PALB2 mutations planning to undergo prophylactic mastectomy is beginning in order to define the toxicity and immunologic effects in this group and to determine whether inflammatory changes from occult lactational foci will be produced. Funding Source: Department of Defense (W81XWH-17-1-0592 and W81XWH-17-1-0593) Table 1 Worst Toxicity by Dose Level Citation Format: Justin Johnson, Emily Rhoades, Holly Levengood, Halle Moore, Megan Kruse, Erin Roesch, Jame Abraham, Brenna Elliott, Rachel Swartz, Holly Pederson, Elena Haury, Azka Ali, Tiffany Onger, Andrew Sciallis, Zahraa Al-Hilli, Wei Wei, Thaddeus Stappenbeck, George Budd. Phase I Trial of alpha-lactalbumin vaccine in high risk operable triple negative breast cancer (TNBC) and patients at high genetic risk for TNBC [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-17-12.

Abstract PO4-22-04: Evaluation of acute toxicity in breast cancer patients receiving concurrent capecitabine and radiation

Abstract Purpose: Adjuvant capecitabine has been shown to improve disease-free survival and overall survival in breast cancer patients who have residual disease after neoadjuvant chemotherapy, particularly in those with triple negative breast cancer (TNBC). While adjuvant chemotherapy is often completed prior to adjuvant radiotherapy (RT), capecitabine may be administered concurrent with RT to reduce the time from surgery to RT. The purpose of this study was to evaluate the feasibility of concurrent therapy and the associated rates of acute loco-regional toxicity. Materials and Methods: A retrospective chart review was performed to identify all breast cancer patients who received adjuvant capecitabine and RT. Patients with a history of prior RT, patients who were treated with capecitabine and RT sequentially, and patients who were treated with palliative intent were excluded. Capecitabine was given Monday-Friday during RT. Patient and disease characteristics, capecitabine and RT treatment details, acute toxicity, and treatment breaks were recorded. Toxicity was scored by the Common Terminology Criteria for Adverse Events (CTCAE) version 5. Results: A total of 27 patients with non-metastatic breast cancer who received concurrent capecitabine and RT with definitive intent treated from 2013 to 2023 were identified. Median age at diagnosis was 52 years [Interquartile Range (IQR) 40-60]. Adjuvant capecitabine dose ranged from 500-1500 mg twice daily. Adjuvant RT dose ranged from 42.56 Gray (Gy) to 50.4Gy. The majority of patients (92.6%) received a sequential 10-14 Gy boost to the lumpectomy site or mastectomy scar, and 70.3% of patients received elective regional nodal RT. During treatment, all patients developed Grade 1 or 2 radiation dermatitis, while Grade 3 radiation dermatitis was noted in 4 (14.8%) patients. Two patients required a treatment break from RT, and both patients were able to subsequently complete their planned RT course. Seven patients (25.9%) required a capecitabine dose reduction or capecitabine treatment break during RT. No Grade 4 or 5 toxicities were reported. Median follow-up from RT completion was 7 months [IQR 0.98-12.2]. At last follow-up, radiation dermatitis had improved to Grade 0-1 for all patients. Conclusion: Concurrent adjuvant capecitabine and RT is a feasible treatment approach that is well tolerated with acceptable acute toxicities. Citation Format: Ahmed Shalaby, Zohaib Sherwani, Lara Hathout, Imraan Jan, Bruce Haffty, Mridula George, Shicha Kumar, Coral Omene, Deborah Toppmeyer, Nisha Ohri. Evaluation of acute toxicity in breast cancer patients receiving concurrent capecitabine and radiation [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-22-04.

Abstract PO1-04-10: Body Mass Index and Treatment Efficacy in advanced Luminal Breast Cancer: Insights from the GEICAM/2013-02 (PEARL) trial

Abstract Background: Endocrine therapy (ET) and treatment directed against molecular targets (CDK 4/6, PI3K, mTOR) constitute the basis of initial treatments for patients with advanced luminal breast cancer. Most of these treatments are oral and have been developed at a fixed dose, without weight adjusted dosing. There is little evidence on the influence that patients’ weight might have on clinical outcomes of these oral drugs in the context of a randomized clinical trial. The present study analyzes the potential impact of the weight of patients treated in the two cohorts of the PEARL trial (NCT02028507) on Progression-Free Survival (PFS), Overall Survival (OS) and the incidence of side effects in each treatment arm. Methods: GEICAM/2013-02 (PEARL) is a multicenter, phase III randomized clinical trial that enrolled patients with hormone receptor-positive/human epidermal growth factor receptor 2-negative metastatic breast cancer (MBC) who progressed to a prior aromatase inhibitor. Patients were randomized 1:1 to receive ET + palbociclib or capecitabine. Patient weight was assessed based on baseline body mass index (BMI) categories: normal (BMI ≤25 Kg/m2), overweight (BMI 25-29.9 Kg/m2) and obesity (BMI ≥30 Kg/m2). Cox's stratified proportional hazard model was used for survival analysis. Adverse events were assessed and graded according to National Cancer Institute common terminology criteria for adverse events (NCI-CTCAE) version 4.0. Results: A total of 600 patients were included in the study and all were evaluable for the weight-based analysis, including 301 in the ET +palbociclib arm and 299 in the capecitabine arm. The distribution of patient’s weights is shown in Table 1. For the Intention-to-treat (ITT) population, no significant difference in the median OS was found between the different weight categories (Normal: 32.8 months vs overweight: 31.9 months, [p=0.467]; obese: 32 months [p=0.407]). Specifically, for patients with normal weight, the median PFS was 9.3 months in the ET + palbociclib group compared to 9.0 months in the capecitabine group (hazard ratio (HR) 0.83, 95% confidence interval [CI]: 0.61-1.13; p=0.23). In the overweight group, the PFS was 7.5 months in the ET+palbociclib group and 11.1 months in the capecitabine group (HR 1.17, 95% CI: 0.87-1.58; p=0.30) while for the obese group, the PFS was 5.7 months vs 11.7 months (HR 1.14, 95% CI: 0.82-1.59; p=0.43), respectively. No substantial differences in the incidence of grade ≥ 3 events were observed when considering weight categories in the different treatment groups (capecitabine arm (Normal: 60%, Overweight: 70.4%, Obese: 61.6%) and ET+palbociclib arm (Normal: 74.5%, Overweight: 76.1%, Obese: 51.6%). Conclusions: Our findings, despite not finding statistically significant differences, suggest a potentially clinically relevant trend towards improved PFS with capecitabine in overweight and obese patients compared to those receiving palbociclib plus ET. The impact of weight on the outcomes with fixed-dose oral drugs warrants further investigation in future studies. Table 1. Citation Format: Manuel Alva, Sara López-Tarruella, Christoph Zielinski, Manuel Ruíz - Borrego, Nicholas Turner, Eva Ciruelos, Montserrat Muñoz, Begoña Bermejo, Mireia Margelí, Antonio Antón, Zsuzsanna Kahan, Tibor Csöszi, Maribel Casas, Laura Murillo, Serafin Morales Murillo, Emilio Alba, Einav Nili-Gal Yam, Angel Guerrero, Lourdes Calvo, Juan de la Haba-Rodríguez, Manuel Ramos, Isabel Álvarez, Andrés García-Palomo, María Koehler, José Ángel García-Sáenz, J. Ignacio Chacón, Claire Swift, Christiane Thallinger, Miguel Gil-Gil, Miguel Martín. Body Mass Index and Treatment Efficacy in advanced Luminal Breast Cancer: Insights from the GEICAM/2013-02 (PEARL) trial [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-04-10.

Safety and Efficacy of Extended Therapy with [177Lu]Lu-PSMA: A German Multicenter Study.

Prospective results have demonstrated favorable safety and efficacy of [177Lu]Lu-PSMA radiopharmaceutical therapy for up to 6 cycles in men with metastatic castration-resistant prostate cancer. However, no systematic data are available outlining the feasibility of extended therapy beyond 6 cycles. We aim to evaluate the safety and efficacy of extended [177Lu]Lu-PSMA radiopharmaceutical therapy in patients who have received more than 6 cycles. Methods: In total, 111 patients were included in this multicenter retrospective analysis. Based on individual decisions, patients underwent uninterrupted continuation of therapy (continuous treatment) or reexposure after a therapy break (rechallenge treatment) between 2014 and 2023. Overall survival, 50% prostate-specific antigen (PSA) decline (measured 8-12 wk after treatment initiation or rechallenge), PSMA PET response, and grades per Common Terminology Criteria for Adverse Events were assessed. χ2 tests, multivariable Cox regression analysis, and log-rank tests were applied for statistical analyses. Results: Patients received extended treatment with [177Lu]Lu-PSMA, either as a continuous treatment (43/111, 38.7%) or as a rechallenge (68/111, 61.3%) treatment, with median cumulative doses of 57.4 or 60.8 GBq, respectively. Overall survival from the initiation of [177Lu]Lu-PSMA was 31.3, 23.2, and 40.2 mo for the entire cohort, the continuous treatment group, and the rechallenge treatment group, respectively. The initial 50% PSA decline was significantly higher in the retreated group than in the continuous group (57/63 [90.4%] vs. 26/42 [61.9%]; P = 0.006). A 50% PSA decline was observed in 23 of 62 patients (37.1%) after the first rechallenge. The rate of grades 3-4 toxicity was comparable between continuous and rechallenge treatments (anemia, 7/43 [16.3%] vs. 13/68 [19.1%)], P = 0.6; leukocytopenia, 1/43 [2.3%] vs. 2/67 [3.0%], P = 0.3; thrombocytopenia, 3/43 [7.0%] vs. 3/68 [4.4%], P = 0.3; renal, 2/43 [4.7%] vs. 5/68 [7.4%], P = 0.2). Conclusion: Extended therapy with [177Lu]Lu-PSMA is safe and has not been associated with increased grades 3-4 toxicity. Patient candidates for extended treatment experienced a favorable median survival of 31.3 mo from the first administration. Response under [177Lu]Lu-PSMA rechallenge demonstrated preserved efficacy of [177Lu]Lu-PSMA after a treatment break.