Treatment-related Toxicity Research Articles

Olaparib, AZD1390, ceralasertib, saruparib and consolidation durvalumab (CONCORDE) phase Ib platform study of novel DNA damage response inhibitor (DDRi) agents in combination with radiotherapy in non-small cell lung cancer (NSCLC).

TPS8119 Background: Lung cancer is the leading cause of cancer mortality globally, with cases projected to exceed 62,000 by 2035. Outcomes remain poor despite advances in radiotherapy (RT) technologies. Combining novel mechanism-based agents with RT could improve the therapeutic index. DNA inhibition of cellular response to radiation-induced DNA damage can overcome intrinsic radio resistance and poses a promising strategy. Methods: CONCORDE is an open label, randomised, multi-arm, phase Ib, clinical trial opened to accrual in 11 UK hospitals designed to assess multiple DDRi in combination with radical thoracic RT (60Gy in 30 fractions over 6 weeks). Patients are randomised 3:1 to RT+/-DDRi. The study utilises an adaptive Bayesian model-based approach to dose escalation aiming to identify the recommended phase II dose for each treatment combination. Two arms will deliver up to 12 months consolidation durvalumab+/-DDRi following RT. Patients are eligible based on key criteria: not suitable for concurrent chemotherapy RT, inoperable, stage IIB/III NSCLC, performance status (KPS≥70). The dose limiting toxicity (DLT) period for treatment-related toxicities is 13.5 months post start of RT treatment, with most toxicities expected within the first 4.5 months (short DLT period). At least one patient must complete the short DLT period before dose escalation. A RT-alone calibration arm aids toxicity attribution. This trial is in progress: CONCORDE-A (olaparib (PARP inhibitor)), CONCORDE-B (AZD1390 (ATM inhibitor)), CONCORDE-C (ceralasertib (ATR inhibitor) followed by consolidation durvalumab+/-ceralasertib) and CONCORDE-E (AZD5305/saruparib (PARP1select inhibitor) followed by consolidation durvalumab) are open to accrual as of 24/11/2023. 57 of 74 registered participants have been randomised across 4 study arms. Of those 57 randomised: 55 started treatment: 20 received RT-alone, 12 received olaparib+RT, 14 received AZD1390+RT, 6 received ceralasertib+RT, 3 received AZD5305+RT and 2 withdrew. CONCORDE continues to recruit to the target sample size of 160 (40/arm) and welcomes further UK centres. A parallel multimodality translational program to identify biomarkers of treatment response, toxicity and the impact on the immune system are in development. Biomarkers of interest include plasma toxicity markers, immune cell profiling, radiomics and ctDNA. Clinical trial information: 10142971.

Standard atezolizumab leads to severe overexposure in real-world patients with lung cancer: How far could we go in extending dosing intervals and saving money?

3085 Background: Immune checkpoint inhibitors are given as fixed doses, which may lead to drug exposure exceeding the plasma concentrations required for target engagement. If confirmed, this could pave the way for de-escalating treatments without compromising efficacy while reducing drug-costs. Methods: We monitored plasma concentrations of Atezolizumab in 40 real-world patients. A final set of 33 patients with SCLC or NSCLC were available for full PK/PD analysis. Individual PK parameters were derived using a population pharmacokinetics approach. Individual PK parameters allowed to simulate the full concentration-time profiles and to further simulate for each patient the time to reach the target threshold after the first dose of Atezolizumab. In addition, efficacy (RECIST criteria) and immune-related adverse events, (IRAEs, CTCAE grading) were monitored and statistical analysis was performed to search for possible exposure-response relationships. Results: Overall Response Rate was 55% and no severe IRAEs were observed. All patients had Cmin levels significantly above the target threshold on the first cycle of Atezolizumab. The mean Cmax after the first dose on cycle 1 was 426.1 µg/ml and the mean Cmin was 68.5 µg/ml, i.e. 11-time higher than the target threshold associated with target engagement (i.e., 6 µg/ml). The mean AUC at the first cycle was 4763 µg.d/ml. Exposure metrics and PK parameters at baseline and simulated prior RECIST evaluation were tested together with other covariates (i.e. age, sex, smoking, NLR, number of metastatic sites, line of treatment) as possible predictive markers of response or toxicity. None of the parameters related to Atezolizumab pharmacokinetics or exposure levels were associated with efficacy or toxicity, most likely because all patients had plasma levels well above pharmacologically active concentrations. First-line therapy was associated with better response on univariate analysis, but this effect was lost on multivariate analysis. Further simulations based on time required to fall below the efficacy threshold suggest that dosing intervals could be extended from Q7W to Q19W (mean: Q12W). Considering the annual budget for Atezolizumab at our institution, further simulations showed that the annual drug cost could thus be reduced from 2.5 M€ to 0.6 M€ while ensuring that all patients remain above active concentrations. Conclusions: Our study demonstrates in a real-world setting that standard Atezolizumab given as 1200 mg Q3W infusion leads to severe overexposure of the drug. This strong overexposure was not associated with more severe treatment-related toxicities. Finally, our study suggests that PK-guided dosing with Atezolizumab could help customizing the dosing interval while maintaining efficacious trough levels and that Q12W could be an alternate scheduling leading to significant cut in drug costs.

Trends in hematopoietic cell transplantation (HCT) in acute myeloid leukemia (AML) from 2004-2019.

6535 Background: Many patients with AML achieve remission after induction chemotherapy, but the relapse rates remain high. For patients with intermediate and adverse-risk AML that have achieved complete remission, HCT often presents the best option for cure. HCT, usually reserved for fit patients with good disease control, comes with different operational, financial, and technical challenges, even in eligible patients. Our study analyzed HCT use in patients with AML from 2004 to 2019 to determine whether the use of HCT has improved in more recent years and identify study subpopulations with an increase in the use of HCT. Methods: Patients with AML from the National Cancer Database were divided into two primary cohorts: patients diagnosed from 2004-2010 and 2011-2019. Logistic regression was used to estimate the effect of patient and disease characteristics on the odds of receiving HCT and evaluate differences between the constructed patient cohorts. Results: Of 78,092 patients with AML, 7204 (9.2%) received HCT. HCT use increased continuously over the years: 6.5% in 2004, 8.4% in 2010, and 10.6% in 2015. There was a slight decrease in HCT from 13.1% in 2018 to 12.2% in 2019. The receipt of HCT declined with increasing age with higher use of HCT in all groups in 2011-2019 compared to 2004-2010: 71-80 years= 2 vs. 0.4 %, 60-70 years= 13 vs 6%, 41-59 years= 18 vs 15%, and 18-40 years = 19 vs 16%. HCT use declined with higher Charlson Deyo Comorbidity Index (CCI) with higher use of HCT in all groups in 2011-2019 compared to 2004-2010: CCI: 2-3= 4 vs 2%, CCI 1= 7% vs 5%, CCI 0= 12% vs 9%. HCT use was higher in patients who traveled longer distances to hospitals with higher HCT use in 2011-2019 compared to 2004-2010: travel distance ≥38.4 miles= 15 vs. 13%, 12-34.7 miles= 12 vs 9%, 5-11.9 miles= 8 vs 5%, and 0-4.9 miles= 5 vs 3%. On multivariable analysis, the odds of receiving HCT increased significantly in 2011-2019 compared to 2004-2010, particularly in older patients, patients with higher CCI, and patients who traveled longer distances for treatment. Black race, lower income, no insurance, and lower educational attainment were associated with a lower likelihood of receiving HCT; however, the odds of receiving HCT did not improve over the two time periods based on these variables. Conclusions: To our knowledge, this is the largest-scale analysis of HCT utilization in patients with AML in the United States. The increase in HCT utilization from 2004-2010 to 2011-2019, particularly in older adults and those with more comorbidities, may reflect improvement in risk-stratification models, better supportive care, and better management of treatment-related toxicity. However, despite a modest increase in HCT use over the years, significant disparities exist based on race, insurance type, income, and education. Innovative strategies are necessary to increase HCT and make it accessible to all patients regardless of socioeconomic and demographic factors.

A United Kingdom prospective, multicentre, observational cohort study investigating tolerance of anti-cancer systemic therapy in the elderly: The TOASTIE study.

1521 Background: Older adults have a higher risk of developing chemotherapy (CTx) related toxicity. The Cancer Aging Research Group (CARG) score was developed and validated in the USA to predict risk of severe CTx induced toxicity in older adults; subsequent validation studies have had varying results. The TOASTIE study sought to evaluate the CARG score prospectively in a United Kingdom (UK) population. Methods: This multicentre, prospective, observational study recruited patients aged ≥65 years commencing first-line neo-adjuvant, adjuvant or palliative CTx for any solid organ malignancy. Those receiving non-CTx agents were excluded. Baseline demographics and established frailty measures were recorded, including Eastern Cooperative Oncology Group performance status (ECOG PS), Rockwood Clinical Frailty Scale (CFS), Geriatric-8 (G8) score and Charlson Co-morbidity Index (CCI). CARG score was calculated after initial Oncology consultation. Follow-up data including CTCAEv5 toxicity and hospital admissions were collected retrospectively. Results: 19 centres recruited 330 patients between Nov 2019 - Dec 2022. Median age was 73 years (range 65-92) and 51.9% were male. 54.9% had a primary tumour of gastrointestinal origin, 48.7% received CTx with palliative intent and 70.8% received doublet therapy. At baseline, 85% patients had an ECOG PS 0 or 1, with median CFS 3 (range 0-8), G8 score 12 (range 6-16) and CCI 6 (range 2-12). Follow-up data was available for 314 (92.6%) patients; the median CTx cycles received was 4 (range 1-16) with 124 (39%) patients dose reduced at cycle one. Treatment delays occurred in 83 (26.4%) patients and 123 (39.2%) stopped treatment early, with 60 (48.8%) cases due to treatment-related toxicity. 69(22.3%) patients experienced a CTCAE grade ≥3 toxicity and 84 (27%) requiring hospital admission. CARG score was available for 313 patients; 107 (34.2%) low risk, 167 (53.4%) medium risk and 39 (12.5%) high risk. Increasing CARG risk groups had increased toxicity rates (low 19.6%, medium 22.2%, high 28.2%) however this was non-significant with no evidence of robust predictive performance (Table). The performance of CFS and ECOG PS was superior to CARG. Conclusions: In this UK older patient population, baseline frailty was prevalent. CARG score was unable to robustly discriminate or predict risk of high-grade toxicity. ECOG showed superior, albeit limited, ability to predict and discriminate toxicity risk. This study highlights the need for development of further tools predictive of toxicity in this population. [Table: see text]

Continuous glucose monitoring and rates of hyperglycemia during chemotherapy for early-stage breast cancer.

e24134 Background: Diabetes (DM) and hyperglycemia (HG) during chemotherapy increase the risk of treatment-related toxicities. The prevalence of HG and daily patterns of HG over the course of chemotherapy in patients with early-stage breast cancer (ESBC) are currently unknown. Methods: We conducted a prospective single-arm pilot study of continuous glucose monitoring in patients with ESBC receiving chemotherapy from 12/2020 – 2/2022. Eligibility criteria included: diagnosis of Stage I-III BC, age ≥18, and planned chemotherapy with concurrent corticosteroid supportive care use. Patients were excluded if they were receiving other systemic corticosteroids or insulin. Patients wore FreeStyle Libre Pro continuous glucose monitoring sensors from the time of chemotherapy initiation (± 7 days) through completion. The sensors detected interstitial glucose levels every 15 minutes and were reapplied by the study team every 2-3 weeks. Primary endpoints were: (1) prevalence of HG, defined as number of patients with ≥1 glucose reading ≥140 mg/dL and (2) among those who developed HG, the proportion of time spent hyperglycemic, defined as number of readings ≥140 mg/dL divided by total number of readings. Key secondary endpoints included prevalence of prediabetes (pre-DM) and diabetes (DM) at baseline and changes in A1c from baseline to weeks 12 and 24. The analysis was stratified by baseline A1c (euglycemia [A1c < 5.7%], pre-DM [A1c 5.7%-6.4%], or DM [A1c ≥6.5% and clinical diagnosis of DM prior to study enrollment]). Results: Among 20 evaluable patients, the median age at baseline was 59 (range 34-78) and median body mass index (BMI) was 29.5 kg/m2 (range 19.5-41.6). The most common chemotherapy regimens included docetaxel/cyclophosphamide (25%), weekly paclitaxel ± trastuzumab (20%), paclitaxel followed by doxorubicin/cyclophosphamide (15%), docetaxel/carboplatin/trastuzumab/pertuzumab (15%), and cyclophosphamide/methotrexate/fluorouracil (15%). All 20 patients developed HG. Of 124,165 total readings, 17% were ≥140 mg/dL and mean glucose was 112.7 mg/dL. At baseline, n = 10 were euglycemic, n = 7 had pre-DM, and n = 3 had DM. By cohort, the proportion of time spent hyperglycemic was 3.9% (euglycemia group), 10% (pre-DM group), and 73.3% (DM group) (p < .0001). Mean glucose values were 95.5 mg/dL (euglycemia group), 104.5 mg/dL (pre-DM group), and 183.0 mg/dL (DM group) (p < .0001). Change in mean A1c from baseline to weeks 12 and 24 varied significantly across groups. Conclusions: Among patients receiving chemotherapy for ESBC, we found evidence of HG in all patients, and the proportion of time spent hyperglycemic during chemotherapy varied significantly by baseline A1c. Further interventions should evaluate the benefits of improved glucose control among patients with baseline A1c > 5.7%. Clinical trial information: NCT04473378 .

A pilot study of early PET and biomarker dynamics in patients with stage 2 and 3 triple negative breast cancer treated with neoadjuvant response-adapted chemotherapy with pembrolizumab (NeoADAPT).

TPS624 Background: In patients with triple negative breast cancer (TNBC) the addition of pembrolizumab to neoadjuvant chemotherapy has improved pathologic complete response rates (pCR) and 5-year event free survival (EFS). Patients with TNBC who achieve a pCR have a significantly lower risk of recurrence compared to those with residual disease (RD). However, pCR can only be assessed at the time of surgery after completion of 6 months of intensive chemo-immunotherapy, associated with up to 77% high-grade treatment-related toxicity. Identifying pCR early on is imperative in developing optimized and individualized treatments, however, there are no predictive biomarkers. Studies in HER2-positive breast cancer have shown that early fluorodeoxyglucose positron emission tomography (FDG-PET) changes soon after initiation of neoadjuvant treatment can help predict the pathological outcomes at the time of surgery and also the risk of recurrence. Emerging data also support that clearance of circulating tumor DNA (ctDNA) during neoadjuvant treatment may be associated with higher rates of pCR. We thus designed a study to determine the association of early FDG-PET changes and ctDNA clearance with pCR in early-stage TNBC. Methods: NeoADAPT is a phase 2, open label, single center clinical trial including adult patients with previously untreated clinical stage 2 or 3 TNBC. Participants will receive 4 cycles of neoadjuvant paclitaxel/carboplatin with pembrolizumab (TC/pembro), per standard-of-care (SOC). An FDG-PET will be performed at baseline and after 1 cycle. A breast MRI will be performed at baseline and after completion of 4 cycles of treatment. Patients with a complete clinical response (cCR) will proceed to surgery and will forgo more neoadjuvant treatment. Patients with clinical RD on MRI will complete SOC neoadjuvant therapy with 4 cycles of doxorubicin/cyclophosphamide (AC) with pembro prior to surgery. If RD is identified after surgery, adjuvant therapy will be determined by the treating oncologist, which may include pembro with AC (if not given prior), capecitabine, etc. The primary objective is to evaluate if lack of decrease in maximum FDG-PET standard uptake value of lean body mass (SULmax) by less than 40% after 1 cycle of neoadjuvant treatment correlates with RD at the time of surgery (i.e. determining the negative predictive value of FDG-PET). Additional key endpoints include ctDNA clearance, evaluation of pCR and cCR rates in the treatment population and EFS. Distributions of percent reduction in SULmax will be compared between pCR and no-pCR groups using the Wilcoxon rank sum test. Receiver operating characteristic (ROC) curve analysis will be performed to estimate the ability of FDG-PET SULmax reduction and cCR by MRI in predicting pCR at surgery. Clinical trial information: NCT06245889 .

A phase I/II study of talazoparib and axitinib in patients with advanced clear cell renal cell carcinoma.

4541 Background: Targeting the VEGF pathway is a backbone therapeutic for patients with advanced clear cell renal cell carcinoma (ccRCC). Tumor and tissue hypoxia may also lead to DNA repair suppression and PARPs are key regulators of DNA damage and genomic maintenance which interact with HIF proteins. Pairing a potent VEGFR TKI with a selective PARP inhibitor (PARPi) may lead to improved outcomes in ccRCC patients. Methods: This was a phase I/II, investigator-initiated, single-center, open-label study (NCT04337970) of talazoparib plus axitinib in previously treated ccRCC patients. In the phase Ib dose escalation, patients must have been previously treated with a PD-1/PD-L1 inhibitor with no maximum lines of prior therapy, and those in dose expansion were required to have prior treatment with a PD-1/PD-L1 inhibitor and prior VEGFR TKI, with a maximum of 2 prior lines of therapy. Patients received escalating doses of talazoparib (0.5 mg, 0.75 mg and 1 mg daily) with axitinib (5 mg twice daily) in a 3+3 design, with primary endpoint of safety and tolerability. After establishing the recommended phase II dose (RP2D), a dose expansion cohort enrolled patients in a Simon two-stage design with a primary endpoint of objective response (ORR), and secondary endpoints including progression-free survival (PFS). Results: From 2020-2023, 23 ccRCC patients were enrolled and treated on study. In the dose escalation, 15 patients enrolled across all 3 dose levels and there were 2 observed DLTS (1 in dose levels 2 and 3). Both DLTs was due to a lack of minimum exposure to study drugs during cycle 1 due to treatment-related toxicities. The maximum tolerated dose and RP2D established was 1 mg talazoparib daily with axitinib 5 mg twice daily. In the phase II dose expansion portion, an additional 9 patients were enrolled to evaluate preliminary efficacy. In total, 13/14 patients treated at the RP2D discontinued therapy due to progressive disease. The objective response rate (ORR) was 7% (90% CI 0, 30), with 1 patient achieving a partial response and 12 patients achieving stable disease (86%). With a median follow-up of 13.2 months (R: 6.6 -29), the median PFS was 6.1 months (95% CI 3.5, 8.4) and median overall survival (OS) was 27 months (95% CI 12- NE). Across the study, 13 (56%) patients had at least one treatment-emergent AE of grade 3+, and 9 (39%) patients had at least one treatment-related AE of grade 3+. Most common grade 3+ AEs included diarrhea, nausea, and anemia. Conclusions: This is the first clinical study evaluating combination PARPi and VEGFR TKI in metastatic ccRCC patients. This study established the RP2D and MTD of combination talazoparib and axitinib and demonstrated a tolerable safety profile across all dose escalation cohorts. The study did not meet the pre-defined efficacy threshold for further enrollment per Simon stage two design. Exploratory efforts to evaluate this treatment approach with tissue biomarker data remain ongoing. Clinical trial information: NCT04337970 .

Phase 1 clinical trial of AMG 340, a prostate-specific membrane antigen (PSMA)-targeted T-cell engager with a novel low-affinity CD3 binding domain designed to mitigate toxicity for the treatment of metastatic castration-resistant prostate cancer (mCRPC).

e14587 Background: PSMA, a transmembrane protein highly expressed on the surface of prostate cancer cells, is a validated target in prostate cancer; however, achieving a favorable therapeutic index has been challenging for PSMA-directed T-cell engagers (TCE’s). AMG 340, a PSMA-targeted TCE with a novel low-affinity CD3 binding domain specifically engineered to mitigate cytokine release syndrome (CRS) toxicity and maintain efficacy was investigated in a phase 1, open-label, dose-escalation study (NCT04740034). Methods: Patients (pts) with mCRPC who had received ≥2 prior lines of therapy were treated with AMG 340 monotherapy (1.5–800 mg intravenously every 3 weeks [Q3W]) during dose escalation. The primary outcome measures were dose-limiting toxicities, treatment-emergent adverse events (TEAEs), and pharmacokinetic profile. Secondary outcomes included prostate antigen specific (PSA) response and objective response per response evaluation criteria in solid tumors (RECIST). Results: As of September 6, 2023, a total of 42 pts (mean ± SD age, 68.5±7.8 years) received AMG 340 step up dosing across 11 cohorts. At doses up to 800 mg Q3W, AMG 340 had a manageable side effect profile. Any grade TEAEs reported in ≥30% of pts included CRS (52%), nausea (52%), vomiting (52%), fatigue (48%), diarrhea (38%), increased aspartate aminotransferase (36%), increased alanine aminotransferase (33%), and hypocalcemia (31%). Treatment-related toxicities included CRS (52%; Grade 1, 26%; Grade 2, 24%; Grade ≥3, 2%) and thrombocytopenia (24%; Grade 2, 10%; Grade ≥3, 14%). Step dosing was implemented at doses >40 mg and successfully mitigated CRS incidence and severity after the first dose. The maximal tolerated dose was not reached, as increasing the dose beyond 800 mg was predicted to minimally increase the potential AMG 340 activity. Exposure increased in an approximately dose-proportional manner with no evidence of clinically significant anti-drug antibodies. AMG 340 demonstrated evidence for pharmacodynamic engagement as shown by cytokine induction. Of the 41 PSA evaluable pts, PSA responses were seen across dose levels (PSA50, n=4), but were not dose dependent. Eight of 42 pts remained on treatment after 6 months. Among 27 RECIST evaluable pts, no RECIST responses were observed (n=14 stable disease, n=0 partial or complete response). Conclusions: Despite reaching high doses, no dose response was observed, and AMG 340 did not generate sufficient clinical activity to warrant further exploration. However, AMG 340 demonstrated manageable CRS toxicity showing that decreased CD3-binding strength mitigates CRS, the main toxicity of TCEs. Clinical studies are ongoing evaluating the PSMA protein as a molecular target for prostate cancer. Clinical trial information: NCT04740034 .

Australian rheumatologists' perception of autologous haemopoietic stem cell transplantation for the treatment of systemic sclerosis: a cross-sectional survey.

Autologous haemopoietic stem cell transplantation (AHSCT) is an effective treatment for systemic sclerosis (SSc); however, treatment-related toxicity remains a key issue. To investigate the perceptions of rheumatologists on the use of AHSCT for SSc. Australian rheumatologists were asked for their opinion on the role of AHSCT, the indications for treatment and the barriers to the use of AHSCT for SSc. A secondary analysis assessed what factors influenced the perception of AHSCT. A total of 77.8% rheumatologists agreed or strongly agreed with the statement that AHSCT is an accepted treatment for SSc. While 65.1% agreed or strongly agreed that treatment-associated mortality was a significant barrier to referral for AHSCT, only 15.2% agreed or strongly agreed that this risk was unacceptable. Progressive lung or skin disease, or lack of response to other therapies, were considered the main referral criteria. A total of 92.0% of respondents agreed or strongly agreed that reduction of treatment toxicity would increase their likelihood to refer patients for AHSCT. Rheumatologists who were aware of the correct evidence base were more likely to consider AHSCT an acceptable treatment for SSc (4.21 ± 0.7 vs 3.64 ± 0.9, P = 0.007). Rheumatologists desire improved patient selection criteria and access to treatment. In this national survey of rheumatologists, AHSCT is considered an accepted therapy. However, concern about toxicity remains a potential barrier to patient referral. Access, studies to refine patient selection and development of AHSCT protocols that improve safety were identified as key areas of need.

Effect of PAWI-2 on pancreatic cancer stem cell tumors.

Worldwide, pancreatic cancer (PC) is a major health problem and almost 0.5million people were diagnosed with PC in 2020. In the United States, more than 64,000 adults will be diagnosed with PC in 2023. PC is highly resistant to currently available treatments and standard of care chemotherapies cause serious side effects. Most PC patients are resistant to clinical therapies. Combination therapy has showed superior efficacy over single-agent treatment. However, most therapy has failed to show a significant improvement in overall survival due to treatment-related toxicity. Developing efficacious clinically useful PC therapies remains a challenge. Herein, we show the efficacy of an innovative pathway modulator, p53-Activator Wnt Inhibitor-2 (PAWI-2) against tumors arising from human pancreatic cancer stem cells (i.e., hPCSCs, FGβ3 cells). PAWI-2 is a potent inhibitor of tumor growth. In the present study, we showed PAWI-2 potently inhibited growth of tumors from hPCSCs in orthopic xenograft models of both male and female mice. PAWI-2 worked in a non-toxic manner to inhibit tumors. Compared to vehicle-treated animals, PAWI-2 modulated molecular regulators of tumors. Anti-cancer results showed PAWI-2 in vivo efficacy could be correlated to in vitro potency to inhibit FGβ3 cells. PAWI-2 represents a safe, new approach to combat PC.

The Efficacy and Tolerability of Radiosurgery in Treating Benign Meningiomas: A Dose Comparison Study from a Single-Center Analysis.

This retrospective study aimed to evaluate the impact of radiation dose on the outcomes of stereotactic radiosurgery (SRS) for benign meningiomas and determine an optimal dosing strategy for balancing tumor control and treatment-related toxicity. Clinical data of 147 patients with 164 lesions treated between 2014 and 2022 were reviewed. Primary outcomes included progression-free survival (PFS), local control rate (LCR), and radiation-induced toxicity, with secondary outcomes focusing on LCR and radiation-induced peritumoral edema (PTE) in two dose groups (≥14 Gy and <14 Gy). The results revealed a median follow-up duration of 47 months, with 1-year, 2-year, and 5-year PFS rates of 99.3%, 96.7%, and 93.8%, respectively, and an overall LCR of 95.1%. Radiation-induced toxicity was observed in 24.5% of patients, primarily presenting mild symptoms. Notably, no significant difference in LCR was found between the two dose groups (p = 0.628), while Group 2 (<14 Gy) exhibited significantly lower PTE (p = 0.039). This study concludes that SRS with a radiation dose < 14 Gy demonstrates comparable tumor control with reduced toxicity, advocating consideration of such dosing to achieve a balance between therapeutic efficacy and safety.

Effect of Radiotherapy on the Right Ventricular Function in Lung Cancer Patients.

Anticancer treatment is associated with many side effects, including those involving the cardiovascular system. While many studies are available on the effects of radiotherapy (RT) on the left ventricle (LV), studies are lacking on the early effects of RT on the structure and function of the right ventricle (RV). Our study aims to assess, using modern echocardiographic techniques, the effect of irradiation on RV systolic function in the mid-term follow-up of patients undergoing RT for lung cancer (LC). This single-center, prospective study included consecutive patients with LC who were referred for treatment with definite radiotherapy and chemotherapy (study group) or chemotherapy only (control group). The study included 43 patients with a mean age of 64.9 ± 8.1 years. Cancer treatment-related RV toxicity (CTR-RVT) was found in 17 patients (40%). Early reductions in TAPSE values were observed among patients in the study group (20.3 mm vs. 22.1 mm, p = 0.021). Compared to baseline, there was a significant reduction in RV global longitudinal strain (RV GLS) in the study group immediately after the treatment (-21.1% vs. -18.4%, p = 0.02) and also at 3 months after RT (-21.1% vs. -19.1%, p = 0.021). A significant reduction in the RV FWLS value was also observed at 3 months after the end of the treatment (-23.8% vs. -21.8, p = 0.046). There were no significant changes in the three-dimensional right ventricular ejection fraction (3DRVEF) during the follow-up. We found a correlation (p = 0.003) between the mean dose of radiation to the RV and 3DRVEF when assessed immediately after RT. The mean dose of radiation to the heart correlated with RV free-wall longitudinal strain (RV FWLS) immediately after RT (p = 0.03). RV cardiotoxicity occurs in nearly half of patients treated for lung cancer. TAPSE is an important marker of deterioration of RV function under LC treatment. Compared to 3DRVEF, speckle tracking echocardiography is more useful in revealing deterioration of RV systolic function after radiotherapy.

Translational risk-adapted approaches to de-escalated radiation for human papillomavirus-positive oropharyngeal cancer: Past, present, and future

Interest in the use of de-escalated radiation to treat patients with newly diagnosed human papillomavirus (HPV)-positive oropharyngeal cancer has grown dramatically with the publication of prospective trials demonstrating the efficacy of such an approach. While the rationale for de-escalation--- namely to decrease treatment-related toxicity while maintaining the excellent rates of disease control historically observed in patients with this disease—is inherently obvious, uncertainty exists regarding how to best select patients for de-escalation. Consequently, risk-adapted strategies using a variety of translational and clinical platforms have been increasingly popularized to better refine treatment. These have integrated contemporary methods of mid-treatment response assessment using advanced technologies and molecular assays to customize the radiation dose. By monitoring the response as patients actively proceed through treatment, risk-adapted protocols have the potential to provide insight into the biological behavior of tumors and make individualized therapy possible. The purpose of this review is to summarize the evidence to date on risk-adapted approaches to de-escalated radiation-- highlighting the clinical, radiological, and biological data which may ultimately help usher the principles of precision medicine into practice for patients with HPV-positive oropharyngeal cancer.

Preferences of physicians for treatment-related toxicity vs. recurrence in melanoma (GERMELATOX-A): the doctors’ perspective

IntroductionAdjuvant treatment with immune checkpoint inhibitors, such as PD1-antibodies (ICI) ± CTLA4-antibodies (cICI) or targeted therapy with BRAF/MEK inhibitors (TT), has shown a significant improvement in disease-free survival (DFS) for high-risk melanoma patients. However, due to specific side effects, the choice of treatment is often influenced by the risk of toxicity. Therefore, the role of physicians in treatment decisions of patients is crucial. This study investigated for the first time in a multicenter setting the attitudes and preferences of dermatooncologists in Germany and Switzerland regarding adjuvant treatment with (c)ICI and TT.MethodsIn the GERMELATOX-A study, 108 physicians (median age: 32 yrs, 67.6% female) from 11 skin cancer centers were surveyed to rate typical side effect scenarios of (c)ICI and TT treatments and then compared to patients’ ratings evaluated in a previous analysis from the same centers. The scenarios described mild-to-moderate or severe toxicity and included melanoma relapse leading to death. The physicians were asked about the level of side effects they would tolerate in exchange for a reduction in melanoma relapse and an increase in survival at 5 years.ResultsThe preferences of physicians and patients revealed significant differences regarding adjuvant melanoma treatment with (c)ICI and TT (p < 0.05). Compared to patients, physicians tend to value a melanoma relapse less severe, according to a visual analog scale. They were also less threatened by all scenarios of side effects during adjuvant treatment with (c)ICI or TT, compared to patients. Physicians required lower risk reductions for disease-free survival (DFS) and overall survival (OS) for both ICI and TT and their drug-related side effects to accept these treatments. In case of severe side effects, physicians required similar 5-year DFS rates for ICI and TT (60–65%), while patients needed a 15% improvement of 5-year DFS for ICI compared to TT (80%/65%). For survival, physicians expected an OS improvement of + 10% for all three treatment modalities, whereas patients required a higher increase: + 18–22% for ICI and + 15% for TT.ConclusionOur study highlights the importance of understanding the patient’s perspective and a potential difference to the doctor’s view when making decisions about adjuvant melanoma treatment with (c)ICI and TT, especially as these treatments are increasingly being implemented in earlier stages.

Cetuximab plus FOLFOXIRI versus cetuximab plus FOLFOX as conversion regimen in RAS/BRAF wild-type patients with initially unresectable colorectal liver metastases (TRICE trial): A randomized controlled trial.

It remains unclear whether intensification of the chemotherapy backbone in tandem with an anti-EGFR can confer superior clinical outcomes in a cohort of RAS/BRAF wild-type colorectal cancer (CRC) patients with initially unresectable colorectal liver metastases (CRLM). To that end, we sought to comparatively evaluate the efficacy and safety of cetuximab plus FOLFOXIRI (triplet arm) versus cetuximab plus FOLFOX (doublet arm) as a conversion regimen (i.e., unresectable to resectable) in CRC patients with unresectable CRLM. This open-label, randomized clinical trial was conducted from April 2018 to December 2022 in 7 medical centers across China, enrolling 146 RAS/BRAF wild-type CRC patients with initially unresectable CRLM. A stratified blocked randomization method was utilized to assign patients (1:1) to either the cetuximab plus FOLFOXIRI (n = 72) or cetuximab plus FOLFOX (n = 74) treatment arms. Stratification factors were tumor location (left versus right) and resectability (technically unresectable versus ≥5 metastases). The primary outcome was the objective response rate (ORR). Secondary outcomes included the median depth of tumor response (DpR), early tumor shrinkage (ETS), R0 resection rate, progression-free survival (PFS), overall survival (not mature at the time of analysis), and safety profile. Radiological tumor evaluations were conducted by radiologists blinded to the group allocation. Primary efficacy analyses were conducted based on the intention-to-treat population, while safety analyses were performed on patients who received at least 1 line of chemotherapy. A total of 14 patients (9.6%) were lost to follow-up (9 in the doublet arm and 5 in the triplet arm). The ORR was comparable following adjustment for stratification factors, with 84.7% versus 79.7% in the triplet and doublet arms, respectively (odds ratio [OR] 0.70; 95% confidence intervals [CI] [0.30, 1.67], Chi-square p = 0.42). Moreover, the ETS rate showed no significant difference between the triplet and doublet arms (80.6% (58/72) versus 77.0% (57/74), OR 0.82, 95% CI [0.37, 1.83], Chi-square p = 0.63). Although median DpR was higher in the triplet therapy group (59.6%, interquartile range [IQR], [50.0, 69.7] versus 55.0%, IQR [42.8, 63.8], Mann-Whitney p = 0.039), the R0/R1 resection rate with or without radiofrequency ablation/stereotactic body radiation therapy was comparable with 54.2% (39/72) of patients in the triplet arm versus 52.7% (39/74) in the doublet arm. At a median follow-up of 26.2 months (IQR [12.8, 40.5]), the median PFS was 11.8 months in the triplet arm versus 13.4 months in the doublet arm (hazard ratio [HR] 0.74, 95% CI [0.50, 1.11], Log-rank p = 0.14). Grade ≥ 3 events were reported in 47.2% (35/74) of patients in the doublet arm and 55.9% (38/68) of patients in the triplet arm. The triplet arm was associated with a higher incidence of grade ≥ 3 neutropenia (44.1% versus 27.0%, p = 0.03) and diarrhea (5.9% versus 0%, p = 0.03). The primary limitations of the study encompass the inherent bias in subjective surgical decisions regarding resection feasibility, as well as the lack of a centralized assessment for ORR and resection. The combination of cetuximab with FOLFOXIRI did not significantly improve ORR compared to cetuximab plus FOLFOX. Despite achieving an enhanced DpR, this improvement did not translate into improved R0 resection rates or PFS. Moreover, the triplet arm was associated with an increase in treatment-related toxicity. ClinicalTrials.gov Identifier: NCT03493048.

Gut Microbiota Are a Novel Source of Biomarkers for Immunotherapy in Non-Small-Cell Lung Cancer (NSCLC).

Despite the recent availability of immune checkpoint inhibitors, not all patients affected by Non-Small-Cell Lung Cancer (NSCLC) benefit from immunotherapy. The reason for this variability relies on a variety of factors which may allow for the identification of novel biomarkers. Presently, a variety of biomarkers are under investigation, including the PD1/PDL1 axis, the tumor mutational burden, and the microbiota. The latter is made by all the bacteria and other microorganisms hosted in our body. The gut microbiota is the most represented and has been involved in different physiological and pathological events, including cancer. In this light, it appears that all conditions modifying the gut microbiota can influence cancer, its treatment, and its treatment-related toxicities. The aim of this review is to analyze all the conditions influencing the gut microbiota and, therefore, affecting the response to immunotherapy, iRAEs, and their management in NSCLC patients. The investigation of the landscape of these biological events can allow for novel insights into the optimal management of NSCLC immunotherapy.

Abstract PO3-19-12: Evaluating the impact of ePRO-based follow-up system (Pink Ribbon Diary) on quality of life and treatment adherence in patients with breast cancer receiving CDK4/6 inhibitors: a single center, randomized controlled study (JPRO-B)

Abstract Background: Treatment-related toxicities (TRT) may decrease patient’s quality of life (QOL) and may result in a decrease of adherence to the therapy. Cyclin-dependent kinase 4/6 inhibitors (CDK4/6is), such as palbociclib (PAL) and abemaciclib (ABM) improved patients’ outcomes with estrogen receptor-positive (ER+) HER2 negative (HER2-) advanced breast cancer (ABC), however, majority of patients who undergo CDK4/6i therapy experience ≥ Grade 2 TRTs, such as hematological abnormalities, gastrointestinal disorders or general fatigue. While prompt management of those TRTs is mandatory to prevent patients from discontinuing the therapy, real-time monitoring of TRTs has been warranted. Recently, efforts have been made to monitor symptoms using electronic patient-reported outcome (ePRO) to detect side effects as early as possible and to provide timely support. However, the efficacy of ePRO in daily clinical practice for those receiving CDK4/6is is still unclear. In addition, the researches in the field of ePRO to date have only focused on drugs administered intravenously in hospitals, where patients’ adherence has no clinical importance. Study design and eligibility criteria: This randomized, open-label, controlled phase 2 trial is designed to assess the efficacy of a new proprietary ePRO system, the Pink Ribbon Diary (PRD), compared with placebo (usual care without the ePRO system) in breast cancer patients with ER+HER2-ABC receiving oral CDK4/6i-based therapy aged ≥ 20 years. All eligible patients who complete training on how to use ePRO system are randomly allocated to either arm A using ePRO system or arm B receiving usual care (1:1). Participants in the arm A are required to record medication taken and physical condition every day for 3 months, and report adverse events using PRO-CTCAETM once a week. Patients in the arm B are also asked to answer to questions concerning adverse events using PRO-CTCAETM at monthly hospital visit for 3 months. All participants are asked to respond to the EORTC QLQ-C30 at their monthly visit and a questionnaire survey on adherence before the study and after completion of the study. Participants in the arm A and healthcare providers, will answer the questionnaire about the feeling of using the PRD. Primary endpoint is the change in global health status/QOL (EORTC QLQ-C30) at 3 months from baseline. Secondary endpoints are RDI (relative dose intensity), other domains of EORTC QLQ-C30, number of days missed medication, PDC (proportion of days covered), survey of medication compliance awareness using MMAS-8 (Morisky Medication Adherence Scale), questionnaire on use of PRD, and comparison between two groups of occurrence of adverse events and incidence of missed medication. Study objective: To assess the clinical efficacy of PRD in patients with ER+HER2-ABC undergoing CDK4/6i-based therapy. Statistical methods: For analysis of QOL, the primary endpoint, the differences in global health status/QOL (EORTC QLQ-C30) before and after the study will be compared between the two groups using the t-test. Present accrual and target accrual: The study was approved by institutional review board in December 2022, and is open for enrollment. The target sample size is 70. The study is on-going and 22 patients have been accrued to date. Trial registration numbers: Japan Registry of Clinical Trials (jRCT) jRCT1030220626 (https://jrct.niph.go.jp/re/reports/detail/30182). Citation Format: Rie Ozeki, Hideo Shimizu, Kotaro Iijima, Misato Okazaki, Junichiro Watanabe, Mitsue Saito. Evaluating the impact of ePRO-based follow-up system (Pink Ribbon Diary) on quality of life and treatment adherence in patients with breast cancer receiving CDK4/6 inhibitors: a single center, randomized controlled study (JPRO-B) [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 PO3-19-12.

Abstract PS14-06: Real-World Analysis of Adverse Events in Patients with Triple Negative Breast Cancer Receiving Therapy per KEYNOTE-522

Abstract Title: Real-world analysis of adverse events in patients with triple-negative breast cancer receiving therapy per KEYNOTE-522 Background: KEYNOTE-522 was a randomized, double-blind, placebo-controlled phase 3 trial which resulted in the FDA approval of pembrolizumab with neoadjuvant chemotherapy for patients (pts) with newly diagnosed, high-risk, early-stage triple-negative breast cancer (TNBC). Given the improvement in pathological complete response (pCR) and event-free survival rates, this regimen has emerged as standard-of-care (SOC) therapy. To date, real world outcome analyses are limited. Methods: In this retrospective, multicenter study, we examined pts with early-stage TNBC who received planned treatment per KEYNOTE-522 as SOC. 16 sites were included in the analysis. IRB approval was obtained from each participating site. Number and length of treatment delays, treatment related toxicities (both chemotherapy and immune-related) of all grades, and pCR rate were collected from the electronic medical record of each participating site, and deidentified data were shared for central analysis. Results: 577 pts were included in this analysis. The median age of the cohort was 52 [range 27-77]. 457 pts had T1-2 disease and 139 had T3-4 disease. 316 pts had N0 disease and 261 had N1-3 disease. 506 pts had baseline ECOG 0, 62 had ECOG 1, and 9 had ECOG 2-3. Of the 482 patients who had surgery at the time of this analysis, 219 patients had pCR (54.5%) and 192 pts were still receiving treatment. 217 patients (37%) had an adverse drug event (ADE) causing dose reductions and 228 patients (39.5%) had to discontinue treatment early. There were 360 unplanned care visits, with 91 patients having 2+ visits. 66 patients had hospitalizations due to the regimen with 102 total hospitalizations. 179 (31%) of patients had grade 3+ immune related adverse events (irAEs), including many that are rare and potentially serious. 317 (54%) had an immune related adverse effect (see Table 1). There was no significant difference in the frequency of grade 3+ irAE based on age or body mass index. We observed no difference in residual disease between patients who discontinued treatment early and those who did not. However, if patients had an ADR causing a dose reduction, pts were significantly more likely to have residual disease (P=0.039) Conclusions: In a multicenter real-world analysis, the KEYNOTE-522 regimen was associated with a high frequency of dose reductions, early treatment discontinuations, ER visits, and hospitalizations. This may have accounted for a lower pCR rate than observed in the landmark clinical trial. Most grade 3+ irAEs occurred at greater frequency in our real-world analysis. Providers should carefully monitor for toxicity to ensure optimal patient outcomes. Table 1 Citation Format: Mara Hofherr, Katherine Clifton, Spenser January, Emily Owen, Farah Raheem, Lida A. Mina, Suganya Arunachalam Karikalan, Lauren Lyons, Meredith Watson Rose, Katherine Madden, Jerline Hsin, Aimee Keegan, Wai Yu, Shawna Kraft, Allison Schepers, Emily Armgardt, Douglas Mazewski, Alison Svoboda, Kayla Harwood, Jodi Taraba, Yonatan Resnick, Shelly Hummert, Lisa Grate, Sidney Keisner, Jacob Hobbs, Todd Davis, Kristin Bastian, Dawn Minikel, Traci White, William Adler, Avneek Singh Sandu, Fouad Boulbol, Kelsey Finch, Andrew Davis. Real-World Analysis of Adverse Events in Patients with Triple Negative Breast Cancer Receiving Therapy per KEYNOTE-522 [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 PS14-06.

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 PS14-02: Real-world analysis comparing Black and White patients with triple-negative breast cancer receiving therapy per KEYNOTE-522

Abstract Abstract Title: Real-world analysis comparing Black and White patients with triple-negative breast cancer receiving therapy per KEYNOTE-522 Background: KEYNOTE-522 was a randomized, double-blind, placebo-controlled phase 3 trial which resulted in the FDA approval of pembrolizumab with neoadjuvant chemotherapy for patients with newly diagnosed, high-risk, early-stage triple-negative breast cancer (TNBC). Despite the significant improvement in pathological complete response (pCR) and event-free survival rates across all patients, the landmark trial included only 4.5% Black patients. It is essential to assess outcomes in representative treatment populations. We assessed real-world toxicity and treatment outcomes across Black and White patients who received standard-of-care treatment per KEYNOTE-522. Methods: In this retrospective, multicenter study, we examined patients with early-stage TNBC who received planned treatment per KEYNOTE-522 as standard-of-care (SOC) therapy. 16 sites were included in the analysis. IRB approval was obtained from each participating site. Number and length of treatment delays, treatment-related toxicities (both chemotherapy and immune-related) of all grades, and pCR rate were collected from the electronic medical record of each participating site, and deidentified data were shared for central analysis. Results: Of the 577 patients who initiated treatment with chemotherapy and immunotherapy, 534 patients were included in this analysis with 105 patients who self-identified as Black (19.7%) and 429 who self-identified as White (80.3%). There were no statistically significant differences in clinical and pathological characteristics between the two groups. White women were more likely to have grade 3+ immune-related adverse events (irAEs) compared to Black women (33.8% vs 20.9%, P=0.011). There was no significant difference across Black and White patients with respect to grade 3+ chemotherapy-related adverse events. Out of the 444 patients who have completed surgery, no difference in pCR rate was observed between Black and White women (45/86 52.3% vs 200/358 55.9%) (p = 0.6). The authors also saw no difference in the rates of hospitalizations between Black and White women (39% vs 36% p = 0.5), and rates of acute care utilization (38% vs 38% p = 0.9). Conclusions: We report safety and efficacy across Black and White women in a real-world analysis of patients who received treatment per KEYNOTE-522. Notably, White patients had a significantly higher frequency of grade 3+ irAEs, although the reason for this finding is unclear based on this analysis. Black patients had similar pCR rates and rates of treatment-related hospitalizations compared to White patients. Assessment of outcomes and toxicity by race in clinical trials and real-world analyses are critical in drug development. Citation Format: Mara Hofherr, Andrew Davis, Spenser January, Emily Owen, Farah Raheem, Lida A. Mina, Suganya Arunachalam Karikalan, Lauren Lyons, Meredith Watson Rose, Katherine Madden, Jerline Hsin, Aimee Keegan, Wai Yu, Shawna Kraft, Allison Schepers, Emily Armgardt, Douglas Mazewski, Alison Svoboda, Kayla Harwood, Jodi Taraba, Yonatan Resnick, Shelly Hummert, Lisa Grate, Sidney Keisner, Jacob Hobbs, Todd Davis, Kristin Bastian, Dawn Minikel, Wiliam Adler, Traci White, Avneek Singh Sandu, Fouad Boulbol, Kelsey Finch, Katherine Clifton. Real-world analysis comparing Black and White patients with triple-negative breast cancer receiving therapy per KEYNOTE-522 [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 PS14-02.