Cycles Of Docetaxel Research Articles

Intensive chemotherapy versus standard chemotherapy among patients with high risk, operable, triple negative breast cancer based on integrated mRNA-lncRNA signature (BCTOP-T-A01): randomised, multicentre, phase 3 trial

ObjectiveTo evaluate the feasibility of using a multigene signature to tailor individualised adjuvant therapy for patients with operable triple negative breast cancer.DesignRandomised, multicentre, open label, phase 3 trial.Setting7 cancer centres...

The New Era of Total Neoadjuvant FLOT Therapy for Locally Advanced, Resectable Gastric Cancer: A Propensity-Matched Comparison With Standard Perioperative Therapy.

The FLOT 4-AIO trial established the docetaxel-based regimen's superiority over epirubicin-based triplet therapy in terms of survival rates and acceptable toxicity for locally advanced resectable gastric (LARGC). Yet, fewer than half of the patients achieved completion of eight prescribed FLOT cycles. We proposed that administering all FLOT cycles in the form of total neoadjuvant therapy may improve completion rates and downstaging. This study contrasted total neoadjuvant therapy (FLOT x8) with standard neoadjuvant therapy (FLOT 4+4) for patients LARGC adenocarcinoma who underwent curative resection with routine D2 lymphadenectomy, focusing on histopathological outcomes, toxicity, and survival outcomes. We reviewed patients with histologically confirmed advanced clinical stage cT2 or higher, nodal positive stage (cN+), or both, with resectable gastric tumors and no distant metastases (January 2017 to July 2023). We divided patients into two groups, FLOT 4+4 and FLOT x8; FLOT 4+4 patients underwent four preoperative and four postoperative bi-weekly cycles of docetaxel, oxaliplatin, leucovorin, and fluorouracil, while FLOT x8 patients received all eight cycles preoperatively after a gradual practice change starting from January 2020. Propensity score matching adjusted for age, clinical stage, tumor location, and histology. Of the 77 patients in the FLOT x8 group, 37 were propensity-matched to an equal number in the FLOT 4+4 group. Demographics, duration of surgery, and hospital stay showed no significant differences between the groups. The FLOT x8 group exhibited a significantly higher all-cycle completion rate at 89.1% compared to FLOT 4+4's 67.6% (p < 0.01). Both groups demonstrated comparable hematological and non-hematological toxicity rates, Clavien-Dindo ≥ 3 complications, and CAP tumor regression grades. The mean number of harvested lymph nodes was 42.5 and 41.2 in the FLOT 4+4 and FLOT x8 groups, respectively. Similar rates of disease-free survival and overall survival were noted in both groups, despite a trend toward a higher pathological complete response rate, albeit not statistically significant (8.1% vs. 18.9%, p = 0.29), in the FLOT x8 group at a median follow-up of 36 months. Total neoadjuvant therapy with the FLOT x8 protocol corresponds to higher treatment completion rates, a safety profile similar to standard perioperative therapy, and a twofold increase in complete pathological response. Further research on long-term oncological outcomes is needed to confirm the effectiveness of total neoadjuvant therapy.

Efficacy and safety of Anlotinib based neoadjuvant chemotherapy for locally advanced triple negative breast cancer (TNBC)

BackgroundAnlotinib, an oral multitarget tyrosine kinase inhibitor, has shown the ability to inhibit tumor angiogenesis. This study aimed to assess the effectiveness and safety of anlotinib plus docetaxel, epirubicin, and cyclophosphamide (TEC) as a neoadjuvant chemotherapy regimen for locally advanced TNBC.MethodsLocally advanced TNBC patients who had received no prior systemic treatment were eligible for this study. The enrolled patients were scheduled to undergo six cycles of anlotinib (12 mg, d1-14, q3w) plus docetaxel (75 mg/m2, d1, q3w), epirubicin (75 mg/m2, d1, q3w) and cyclophosphamide (600 mg/m2, d1, q3w) prior to surgery, unless there was disease progression or severe toxicity. The primary objective of this study was the safety of this therapeutic regimen, and the secondary objective was the tumor response. The safety of this regimen was assessed using Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 and the efficacy of this treatment was measured using the Response Evaluation Criteria in Solid Tumors version 1.1.ResultsA total of 18 patients were included in this study. Participants completed an average of 5.56 neoadjuvant treatment cycles. The objective response rate (ORR) was 83.33%, and the disease control rate was 100%, respectively. The pCR was 55.6%. No patients discontinued therapy because of Adverse effects (AEs). Grade 3 or 4 AEs were observed in 5 cases (27.8%), with neutropenia and palmar-plantar erythrodysesthesia syndrome being the most common.ConclusionsAnlotinib combined with TEC as neoadjuvant therapy demonstrated manageable toxicity and promising antitumor activity for locally advanced TNBC. Further investigation of this combination regimen is warranted.

Drug induced lupus associated with Trastuzumab emtansine in a patient with metastatic breast cancer

Introduction Ado-trastuzumab emtansine (T-DM1) is employed in the treatment of patients with HER2-positive breast cancer. The most common side effects are fatigue, diarrhoea, anaemia, transaminase elevation and drug-induced thrombocytopenia. This report describes a patient with metastatic breast cancer who developed drug-induced lupus due to T-DM1. Case Report A 54-year-old woman was diagnosed with breast cancer in March 2018. She underwent modified radical mastectomy and axillary lymph node dissection (pT2N1aM0). Following supraclavicular lymph node metastasis in May 2018, she received 8 cycles of docetaxel, trastuzumab, and pertuzumab. In December 2020, the patient presented with axillary and intra-abdominal lymph node metastases, along with bone metastases observed on PET/CT scan. Treatment with T-DM1 and zoledronic acid was initiated. After 18 months on T-DM1, she developed drug-induced lupus. Her symptoms resolved with hydroxychloroquine treatment and discontinuation of T-DM1. Discussion Drug-induced lupus is a clinical syndrome that shares similar features with systemic lupus erythematosus (SLE). The majority of patients present with symptoms such as arthralgia and myalgia. Hydralazine and procainamide are high-risk drugs for drug-induced lupus. Symptoms usually develop after months or years of use, but may also develop suddenly. Our patient also received TDM-1 treatment for 18 months. We present a case of TDM-1-associated drug-induced lupus in a patient with metastatic breast cancer. This is the first case of TDM-1-related drug-induced lupus reported in the literature.

Sequential [177Lu]Lu-PSMA-617 and docetaxel versus docetaxel in patients with metastatic hormone-sensitive prostate cancer (UpFrontPSMA): a multicentre, open-label, randomised, phase 2 study

Lutetium-177 [177Lu]Lu-prostate-specific membrane antigen (PSMA)-617 improves survival and quality of life in patients with metastatic castration-resistant prostate cancer, but whether it confers a benefit in hormone-sensitive disease is unknown. We aimed to evaluate [177Lu]Lu-PSMA-617 before docetaxel treatment in patients with de-novo high-volume metastatic hormone-sensitive prostate cancer. UpFrontPSMA was an investigator-initiated, multicentre, open-label, randomised, phase 2 trial done at 11 Australian hospitals. Eligible patients had prostate adenocarcinoma without clinically significant neuroendocrine differentiation or small-cell histology, were aged 18 years or older, had less than 4 weeks on androgen deprivation therapy, had an Eastern Cooperative Oncology Group performance status of 0-2, and had high-volume PSMA-avid disease on [68Ga]Ga-PSMA-11 PET-CT with no major discordance on 2-[18F] fluorodeoxyglucose-PET-CT. Patients were randomly assigned (1:1) to the experimental treatment ([177Lu]Lu-PSMA-617 followed 6 weeks later by docetaxel) or standard-of-care treatment (docetaxel alone) using computer-based block randomisation with random block sizes, stratified by disease volume by conventional imaging and duration of androgen deprivation therapy at the time of registration. Neither patients nor investigators were masked to treatment assignment. Patients in the experimental group received two cycles of [177Lu]Lu-PSMA-617 7·5 GBq every 6 weeks intravenously, followed 6 weeks later by six cycles of docetaxel 75 mg/m2 every 3 weeks intravenously, whereas patients in the standard-of-care treatment group received six cycles of docetaxel 75 mg/m2 every 3 weeks intravenously. All patients received continuous androgen deprivation therapy. The primary endpoint was undetectable prostate-specific antigen (≤0·2 ng/mL) at 48 weeks, assessed using a modified intention-to-treat analysis. The trial is registered with ClinicalTrials.gov, NCT04343885. Between May 5, 2020, and April 18, 2023, 130 patients were randomly assigned, 63 (48%) to [177Lu]Lu-PSMA-617 plus docetaxel and 67 (52%) to docetaxel alone. All patients were male and no race or ethnicity data were collected. Median follow-up was 2·5 years (IQR 1·8-3·0). Four patients in the docetaxel alone group withdrew consent after randomisation and no data beyond screening were collected. An additional four patients were not evaluable for the primary endpoint at 48 weeks (two in each group). 25 (41%) of 61 patients (95% CI 30-54) in the [177Lu]Lu-PSMA-617 plus docetaxel group had undetectable PSA at 48 weeks compared with ten (16%) of 61 patients (9-28) in the docetaxel alone group (OR 3·88, 95% CI 1·61-9·38; p=0·0020). The most common grade 3 or 4 treatment-related adverse events were febrile neutropenia (seven [11%] of 63 patients in the [177Lu]Lu-PSMA-617 plus docetaxel group vs six [10%] of 63 patients in the docetaxel alone group) and diarrhoea (four [6%] of 63 patients vs none). Serious adverse events occurred in 16 (25%) patients in the [177Lu]Lu-PSMA-617 plus docetaxel group (none were definitely related to [177Lu]Lu-PSMA-617) and 16 (25%) patients in the docetaxel alone group. No treatment-related deaths occurred. [177Lu]Lu-PSMA-617 followed by docetaxel improved antitumour activity in patients with de-novo high-volume metastatic hormone-sensitive prostate cancer compared with docetaxel alone, without increased toxic effects. Our data potentially support a role for [177Lu]Lu-PSMA-617 in metastatic hormone-sensitive prostate cancer. Prostate Cancer Research Alliance (Movember Foundation and Australian Government Medical Research Future Fund), US Department of Defence Impact Award-Clinical Trials, Endocyte/Advanced Accelerator Applications (a Novartis company), Australian Nuclear Science and Technology Organization, Victorian Cancer Agency, University of Melbourne, and Peter MacCallum Cancer Foundation.

Trastuzumab-induced optic neuritis: "blindness" side effect.

Trastuzumab improved the prognosis of patients with human epidermal growth factor receptor 2 (HER2)+ breast cancer (BC). Here, we present a patient who developed acute vision loss due to optic atrophy in both eyes after trastuzumab. A 60-year-old female patient was diagnosed with locally advanced HER2+ BC in January 2021. After four cycles of neoadjuvant anthracycline-based chemotherapy followed by four cycles of docetaxel, trastuzumab, and pertuzumab combined treatment, the patient underwent a right modified radical mastectomy. Three days after the end of the second cycle of adjuvant trastuzumab, she presented with acute vision loss. The patient's visual acuity was 90% in the right eye and 60% in the left eye. The left eye had optic nerve edema and spindle hemorrhages. First, on suspicion of optic neuritis, the patient was given a 1 gram/day pulse steroid for three days. However, optic neuritis was not considered during the follow-up. Metastasis was considered at the exit of the left optic nerve. Trastuzumab was started by making a mutual decision with the patient. Six days after the sixth dose of adjuvant trastuzumab, she presented with almost complete vision loss. The patient was diagnosed with optic neuritis, and a pulse steroid was administered. Trastuzumab was permanently discontinued. However, the patient's visual acuity in both eyes remained at 5-10%. Vision loss due to optic neuritis is a devastating side effect. Understanding that trastuzumab-induced optic neuritis may develop will help clinicians detect side effects early and manage them more effectively.

Long-Term Outcomes of Adjuvant Trastuzumab for 9 Weeks or 1 Year for ERBB2-Positive Breast Cancer

The standard adjuvant treatment for patients with ERRB2-positive breast cancer is chemotherapy plus 1 year of trastuzumab. Shorter durations of trastuzumab administration improve cardiac safety, but more information is needed about their effect on survival. To compare survival outcomes after 9-week vs 1-year administration of trastuzumab with the same adjuvant chemotherapy. This post hoc secondary analysis of an open-label, multicenter, noninferiority-design randomized clinical trial included women aged 18 years or older with early ERBB2-positive, axillary node-negative or axillary node-positive breast cancer who were enrolled from January 3, 2008, to December 16, 2014, at 65 centers in 7 European countries. The current exploratory analysis was conducted after achieving the maximum attainable follow-up data when the last patient enrolled had completed the last scheduled visit in December 2022. Chemotherapy consisted of 3 cycles of docetaxel administered at 3-week intervals followed by 3 cycles of fluorouracil, epirubicin, and cyclophosphamide at 3-week intervals. Trastuzumab was administered in both groups for 9 weeks concomitantly with docetaxel. In the 9-week group, no further trastuzumab was administered after chemotherapy, whereas in the 1-year group, trastuzumab was continued after chemotherapy to complete 1 year of administration. The primary objective was disease-free survival (DFS). Distant DFS and OS were secondary objectives. Survival between groups was compared using the Kaplan-Meier method and log-rank test or univariable Cox proportional hazards regression. Among the 2174 women analyzed, median age was 56 years (IQR, 48-64 years). The median follow-up time was 8.1 years (IQR, 8.0-8.9 years); 357 DFS events and 176 deaths occurred. Trastuzumab for 9 weeks was associated with shorter DFS compared with trastuzumab for 1 year (hazard ratio [HR], 1.36; 90% CI, 1.14-1.62); 10-year DFS was 80.3% in the 1-year group vs 78.6% in the 9-week group. The 5-year and 10-year OS rates were comparable between the 9-week and 1-year groups (95.0% vs 95.9% and 89.1% vs 88.2%, respectively; HR for all time points, 1.20; 90% CI, 0.94-1.54). In multivariable analyses, 9-week treatment was associated with shorter DFS compared with 1-year treatment (HR for recurrence or death, 1.36; 95% CI, 1.10-1.68; P = .005), but there was no between-group difference in OS (HR, 1.22; 95% CI, 0.90-1.64; P = .20). Only 4 patients (0.2%) died of a cardiac cause. In this secondary analysis of a randomized clinical trial, 1-year vs 9-week adjuvant trastuzumab was associated with improved DFS among patients with ERRB2-positive breast cancer receiving chemotherapy, but there was no significant difference in OS between the groups. ClinicalTrials.gov Identifier: NCT00593697.

Adjuvant chemotherapy guided by an integrated mRNA–lncRNA signature in triple-negative breast cancer (BCTOP-T-A01): A randomized, open-label, multicenter phase 3 trial.

525 Background: Triple-negative breast cancer (TNBC) is a highly heterogeneous disease with variable clinical outcomes. We have previously classified patients with TNBC into high- and low-risk groups based on a multigene signature. In this study, we aimed to evaluate the feasibility of utilizing a multigene signature to tailor individualized adjuvant therapy for patients with operable TNBC. Methods: This multicenter, open-label, randomized, phase 3 trial was conducted at 7 cancer centers in China. We included female patients aged 18-70 years with early TNBC after definitive surgery (histologically confirmed axillary lymph node-positive or lymph node-negative with tumor diameter &gt;10 mm). After categorization using the integrated signature, high-risk patients were randomized (1:1) to receive an intensive adjuvant treatment comprising four cycles of docetaxel, epirubicin, and cyclophosphamide followed by four cycles of gemcitabine and cisplatin (TEC-GP; arm A), or the standard four cycles of epirubicin and cyclophosphamide followed by four cycles of docetaxel (EC-T; arm B). Low-risk patients received the same adjuvant chemotherapy as arm B (arm C). The primary endpoint was disease-free survival (DFS) in the intention-to-treat analysis of arm A versus arm B. Results: Between January 2016 and July 2023, 504 patients (336 high-risk and 168 low-risk; median age, 52 years; 488 with T1-2 tumors; 263 with node-positive disease) were recruited. At a median follow-up of 45.1 months, the 3-year DFS rates were 90.9% for patients in arm A and 80.6% for patients in arm B (hazard ratio [HR], 0.51; 95% confidence interval [CI], 0.28 to 0.95; P = 0.030). Intensive chemotherapy improved DFS relative to standard therapy irrespective of tumor size and nodal status. The 3-year RFS was 92.6% in arm A and 83.2% in arm B (HR, 0.50; 95% CI, 0.25 to 0.98; P = 0.039). The groups did not differ in OS (HR, 0.58; 95% CI, 0.22 to 1.54; P = 0.267; 3-year OS, 98.2% vs 91.3%). Upon receiving the same chemotherapy regimen, patients in arm C had significantly higher DFS (HR, 0.57; 95% CI, 0.33-0.98; P = 0.038; 3-year DFS, 90.1% vs 80.6%), RFS (HR, 0.42; 95% CI, 0.22-0.81; P = 0.007; 3-year RFS, 94.5% vs 83.2%) and OS (HR, 0.14; 95% CI, 0.03-0.61; P = 0.002; 3-year OS, 100% vs 91.3%) compared to patients in arm B. The incidence of grade 3 to 4 treatment-related adverse. events for arms A, B and C, respectively, were thrombocytopenia (14.1%, 2.5%, 1.8%), febrile neutropenia (9.9%, 4.3%, 4.9%), anemia (5.8%, 1.9%, 1.8%), nausea (7.0%, 3.7%, 4.9%), vomiting (8.3%, 4.3%, 4.9%) and myalgia (2.6%, 5.6%, 5.5%). There were no treatment-related deaths. Conclusions: The multigene signature showed potential for tailoring adjuvant chemotherapy for patients with operable TNBC. Intensive regimens incorporating GP into anthracycline/taxane-based therapy improves survival with manageable toxicity. Clinical trial information: NCT02641847 .

A phase II trial of neoadjuvant docetaxel/5-FU/cisplatin in combination with prophylactic pegteograstim in unresectable, locally advanced nasal cavity/paranasal squamous cell carcinoma: KCSG HN18-07.

6020 Background: Squamous cell carcinoma (SCC) arising from paranasal sinus and nasal cavity (PNSNC) is often diagnosed at locally advanced stage. Neoadjuvant strategies have been explored to improve prognosis and facilitate organ preservation. The efficacy of triplet neoadjuvant chemotherapy (NAC) has not been established prospectively. We conducted a phase II trial of neoadjuvant docetaxel/5-FU/cisplatin (DFP) combined with prophylactic pegteograstim in unresectable, locally advanced PNSNC (KCT0003377). Methods: Eligible patients had unresectable SCC of PNSNC, were aged 19-75, had an ECOG performance status of 0/1, and demonstrated adequate organ function. Patients with distant metastasis were excluded. Criteria for unresectability included tumor or lymph node fixation, clinical T3/4 stage, or potential compromise of critical organ function (e.g., necessitating eyeball exenteration). NAC comprised three cycles of docetaxel (75mg/m2 on Day 1), cisplatin (75mg/m2 on Day 1, 60mg/m2 for those aged ≥65), and 5-FU (1,000mg/m2 on Days 1-4) administered every 3 weeks. Prophylactic pegteograstim (6mg) was administered on Day 6 or 7. The primary outcome was the overall response rate (ORR), with secondary outcomes including progression-free survival (PFS), the eyeball preservation rate at 24 months, and safety. The study required 28 patients to achieve a power of 80% (P0=0.45, P1=0.70, α-error=0.05, 10% dropout rate). Results: Between 2019 and 2023, 28 patients were screened, and 27 received at least one cycle of NAC. The median age was 58 years (range: 41-71), with 24 males. Seventeen had maxillary sinus origin, and ten had nasal cavity origin. Twenty-two patients had T4 disease, and six had N2 disease. The ORR was 64.3% (5 complete responses, 13 partial responses). Post-NAC treatments included surgery alone (n=2), concurrent chemoradiotherapy (CCRT) (n=15), surgery followed by CCRT (n=2), or radiotherapy (RT) (n=5). Procedures performed were total maxillectomy (n=4), partial maxillectomy (n=3), and endoscopic sinus surgery (n=2). With a median follow-up of 21.5 months (range: 0.1-53.0), the 2-year PFS and eyeball preservation rate were 64% and 100%, respectively. Fourteen patients experienced Grade ≥3 adverse events (AEs): hematologic (46.4%), non-hematologic (14.3%), with Grade 3/4 neutropenia (32.1%) and febrile neutropenia (14.3%). Dose reduction or delay occurred in 9 patients (33.3%). One patient died on Day 6 of cycle 1. Conclusions: DFP NAC demonstrated promising efficacy and an excellent eyeball preservation rate with manageable toxicity. DFP NAC with prophylactic pegteograstim, could be a reasonable option for patients with locally advanced SCC of the PNSNC. Follow-up is ongoing. Clinical trial information: KCT0003377 .

Personalized neoadjuvant strategy in ER positive and HER2 negative breast cancer to increase BCS rate (PLATO): A prospective, multicenter, phase II clinical trial.

595 Background: Neoadjuvant therapy significantly enhances the likelihood of breast-conserving surgery (BCS) in breast cancer patients. However, in ER-positive and HER-2 negative breast cancer, the response to neoadjuvant chemotherapy (NCT) is not as good as HER-2 positive or triple-negative breast cancer. In addition, with the evolution of multi-gene assays, many patients of this subtype may not require adjuvant chemotherapy. This study explores the potential of tailored neoadjuvant treatments (NCT or endocrine therapy (NET)) guided by 70-gene assay (Mammaprint, Agendia) to improve BCS rates in ER-positive/HER-2 negative breast cancer. Methods: A prospective, multicenter cohort study was conducted across four Korean centers from 2019 to 2023. Participants were clinical stage II-IIIA, ER-positive/HER2-negative breast cancer patients deemed unsuitable for BCS. Suitability was further verified by an independent three-surgeon panel using mammography or MRI. Out of 130 screened patients, 100 were enrolled. We analyzed 90 patients, excluding 10 cases; 2 with a basal type or HER2 type result in the blueprint, 7 who refused neoadjuvant therapy, and 1 who underwent surgery at another hospital. Before initiation of therapy, each surgeon recorded a target tumor size at which the surgeon would be able to do BCS considering location of the tumor and patient’s breast size. Based on the 70-gene assay results from core needle biopsies, high-genomic-risk patients received NCT (anthracycline + cyclophosphamide for 4 cycles, followed by 4 cycles of docetaxel), while low-risk patients underwent 16 weeks of NET with letrozole (±leuprolide for premenopausal women). Results: Out of the patients, 66 (73%) were high-genomic-risk and underwent NCT, while 24 (27%) received NET. Median tumor size was 3.7cm (85.6% clinical T2 and 14.4% T3/4). The primary endpoint, achieving the pre-established target tumor size for BCS, was reached by 70.0% (95% CI: 59.4-79.2%) of patients, significantly surpassing the set goal of 50.8% (a 15% increase from historical control). The rates were 74.2% for NCT and 58.3% for NET. The actual BCS rate was 58.9% overall (63.6% for NCT and 45.8% for NET). Clinically, 5.6% exhibited complete response (CR), 74.4% partial response (PR), 18.8% stable disease (SD), and 1.1% progressive disease (PD). Pathologic complete response (pCR) was achieved in 2.2% (all in the NCT group). No severe adverse events beyond expectations were observed. No pre-treatment clinical or pathological factor was significantly predictive for the BCS conversion. Conclusions: For ER positive, HER2 negative breast cancer patients initially ineligible for BCS, the use of pre-treatment multi-gene assays to guide selective NCT or NET could substantially increase BCS rates and reduce unnecessary chemotherapy. Clinical trial information: NCT03900637 .

A phase II study of radiotherapy combined with docetaxel, cisplatin, and 5-fluorouracil for postoperative loco-regional recurrent esophageal cancer.

4029 Background: Recently, neoadjuvant chemotherapy or chemoradiotherapy followed by surgery for patients with esophageal cancer have resulted in favorable prognosis, but extended radical esophagectomy with two-field or three-field (neck, mediastinum, and abdomen) lymph node dissection remains a standard treatment. However, there is recurrence in 30-50% of patients who have undergone an operation and there is loco-regional recurrence in 40-55% of patients with postoperative recurrence. The efficacy and safety of chemoradiotherapy for postoperative loco-regional recurrent esophageal cancer have been reported, and the survival outcome has been improved; however, the median progression-free survival period according to past reports was 10 to 14 months, which was not enough. Recently, RT with docetaxel (DOC), cisplatin (CDDP) and 5-FU has shown better results than conventional standard treatment (CDDP+5-FU +radiotherapy) for primary esophageal cancer. The purpose of the phase II study was to evaluate the superior of definitive radiotherapy with DOC, CDDP and 5-FU to the standard treatment in patients with loco-regional recurrent esophageal cancer after curative resection. Methods: Between 2015 and 2023, this open-label, single-arm, phase II study of radiotherapy (60 Gy/30 fractions/6 weeks without prophylactic region) combined with chemotherapy consisting of 3 cycles of DOC (35 mg/m2), CDDP (40 mg/m2) and 5-FU (400 mg/m2/24 h for 5 days) for patients with postoperative loco-regional recurrent esophageal cancer was conducted at a single institution. The primary endpoint was progression-free survival rate. This trial was considered positive if median progression-free survival period was 24.0 months or more, which meaning superiority over conventional standard treatment. The secondary endpoints were overall survival rate and adverse events. This trial was registered with UMIN Clinical Trials Registry (UMIN000019269) and Japan Registry of Clinical Trials (jRCTs021200009). Results: A total of 29 patients were enrolled in this study. The regimen was completed in all the patients. The median observation period for survivors was 60 months (IQR, 30.0-75.5 months). The 5-year progression-free survival rate was 56.2% (95% CI = 37.4-75.0%) with a median progression-free survival period of 62.0 months (95% CI = 35.2-64.7 months). Only 2 patients showed grade 4 hematologic adverse events during chemoradiotherapy, and they had to be performed reduced chemotherapy; however, they also completed 3 cycles of concurrent chemotherapy. Grade 2 or higher late toxicity was not observed in any patients. Conclusions: The present protocol of radiotherapy combined with DOC, CDDP and 5-FU is a safe and effective salvage treatment for postoperative loco-regional recurrent esophageal cancer. It might be better than conventional treatment. Clinical trial information: UMIN000019269.

Neoadjuvant docetaxel, oxaliplatin, and S-1 plus surgery followed by adjuvant docetaxel and S-1 for patients with large type 3 or type 4 gastric cancer: Short-term outcomes of the phase II OGSG1902 trial.

4031 Background: Patients with large type 3 (≥8 cm) or type 4 gastric cancer (GC) face a dismal prognosis, necessitating the development of multidisciplinary treatment, including neoadjuvant chemotherapy. We present the short-term results from the OGSG1902 (jRCTs051190060) trial, where resectable large type 3 or type 4 GC patients were treated with neoadjuvant docetaxel (DTX)/oxaliplatin (L-OHP)/S-1 (DOS) plus surgery and adjuvant DTX/S-1 (DS) therapy. Methods: Untreated large type 3 or type 4 GC patients without distant metastasis other than positive peritoneal lavage cytology (CY), aged 20-80 years, and with ECOG PS 0-1, were enrolled. Patients received three cycles of DTX (40 mg/m2, day1) + L-OHP (100 mg/m2, day1) + S-1 (80 mg/m2, day1-14) every 3 weeks, followed by gastrectomy with D2 lymph node dissection and 1-year DS therapy. The primary end point was the 3-year progression-free survival (PFS) rate. The secondary end points included PFS time, overall survival time, pathological response rate, response rate according to RECIST version 1.1, neoadjuvant chemotherapy completion rate, R0 resection rate, protocol completion rate, CY negative conversion rate, adverse event occurrence rate, and nutritional evaluation. Results: Forty-eight patients (pts) were enrolled from 2019 to 2022. The neoadjuvant chemotherapy completion rate was 91.7%, pathological response rate (≥Grade 1b) was 66.7%, response rate according to RECIST version1.1 for 10 pts with measurable lesions was 50.0%, CY negative conversion rate for nine CY positive pts was 88.9%, R0 resection rate was 89.6%, and the protocol completion rate was 45.8%. Adverse events (≥CTCAE Grade 3) during neoadjuvant DOS included neutropenia in 18 pts (38%), febrile neutropenia in one pt (2%), nausea in five pts (10%), diarrhea in six pts (13%), and anorexia in 18 pts (38%). Gastrectomy was performed in 47 pts [total/distal gastrectomy: 32(68%)/15(32%)]. Major postoperative complication (≥Clavien-Dindo Grade IIIa) was observed in one pt (2%), including pleural infection. Adverse events (≥CTCAE Grade 3) in 39 patients receiving adjuvant DS therapy included neutropenia in 16 pts (41%), anemia in five pts (13%), nausea in one pt (3%), diarrhea in two pts (5%), anorexia in nine pts (23%), fatigue in three pts (8%), and febrile neutropenia in four pts (10%). No treatment-related deaths were observed. Conclusions: Neoadjuvant DOS therapy for large type 3 or type 4 GC demonstrates promising efficacy with high histological response and acceptable adverse events. Future analysis of survival outcomes is planned. Clinical trial information: jRCTs051190060 .

Neoadjuvant chemotherapy combined with PD-1 inhibitor for laryngeal preservation in locally advanced hypopharyngeal squamous cell carcinoma: A single-arm, phase II clinical trial.

e18035 Background: Neoadjuvant chemotherapy (NCT) combination with PD-1 inhibitor has a significant efficacy and approved indications in the first-line treatment of R/M head and neck squamous cell carcinoma (HNSCC), but the efficacy of the combination therapy in locally advanced hypopharyngeal squamous cell carcinoma (HPSCC) remains unexplored. This study aimed to explore the efficacy and safety of NCT with PD-1 inhibitor for laryngeal preservation in patients with HPSCC. Methods: Patients with cT1N1-3M0 or cT2-3N0-3M0 (AJCC 8th) were eligible after multidisciplinary team (MDT) discussion. All patients received 2 cycles of intravenous docetaxel (60mg/m2 on d1), cisplatin (60mg/m2 on d1), fluorouracil (600mg/m2 per day as a continuous 120h infusion on d1-5) and toripalimab (240mg on d1) every 21 days. And the MDT underwent efficacy evaluation according to RECIST 1.1. Patients with complete response (CR)/partial response (PR) of the primary lesion(P) and no progressive disease (PD) in neck lymph nodes (LN) received definitive radiotherapy (RT) combined with toripalimab. Patients with stable disease (SD)/PD of P and no PD in LN or with PD in LN underwent surgery. Patients completed the third cycle of neoadjuvant therapy(NAT) before RT or surgery. The primary endpoint was the CR rate at 3 months (3m-CR) after NAT and definitive RT, and the secondary endpoints were the objective response rate (ORR) of NAT, laryngeal preservation rate, and adverse effects(AE). The sample size was calculated by the Simon-II-stage method: 27 patients in first stage (if ≥9 patients got 3m-CR, second stage started) , and a cumulative total of 81 patients in second stage. Results: From October 2020 to August 2023, 23 patients (median age:59, range:51-69, male:100%, stage II/III/IVA/IVB:4.3%/4.3%/26.1%/65.2%) were enrolled. After NAT, the ORR of primary tumor was 78.3% (18/23, including 2 CR), the ORR of lymph node was 65.2%% (15/23, including 9 CR), and the overall ORR was 70.0% (16/23). Fifteen patients received non-surgical treatment after NAT, and 8 patients underwent surgery (6 underwent laryngeal preservation surgery). At 3 months after RT or surgery, 18 patients completed evaluation. The CR rate was 77.8%, and the laryngeal preservation rate was 88.9%. In 13 evaluable patients who received NAT followed by definitive RT, 10 patients (76.9%) had an overall response of 3m-CR. During the NAT, 43.5% (10/23) of patients experienced grade 3-4 AEs, with grade 3-4 leukopenia or neutropenia in 30.4% (7/23) and grade 3 immune enteritis in 13.0% (3/23). Conclusions: NCT combination with PD-1 inhibitor may improve the ORR of HPSCC, potentially further increasing the laryngeal preservation rate, with manageable treatment-related AEs. The study results are pending publication after completion of the enrollment. Clinical trial information: NCT04624308 .

The Association of Docetaxel Side Effects and Introduction of Subsequent Cabazitaxel for Castration-Resistant Prostate Cancer : A Clinical Study

The administration of cabazitaxel for patients with castration-resistant prostate cancer (CRPC) requires prior docetaxel therapy. Sequential chemotherapy may have to be discontinued due to docetaxelassociated side effects. This study investigated the relationship between treatment outcome of docetaxel and cabazitaxel and their associated side effects. We retrospectively analyzed 69 patients with CRPC who had been administered docetaxel withand without subsequent cabazitaxel at Toyonaka Municipal Hospital from October 2014 to June 2022. Twenty-eight patients (41%) discontinued docetaxel because of side effects, and the median number of docetaxel cycles at discontinuation was 2 (range : 1-11). Fourteen of these patients received no treatment following docetaxel. A comparison of the 28 patients who had discontinued docetaxel due to side effects with 41 patients who had not revealed a significant difference in the total numbers of chemotherapy cycles (2.5 vs 9 ; P＜0.001) and time to treatment failure (56 days vs 301 days ; P＝ 0.001), with a trend toward shorter overall survival from the start of docetaxel treatment (259 days vs 512 days ; P＝0.06). Multivariate analysis identified discontinuation of docetaxel due to side effects (OR＝0.07 ; P＜0.001) and lower hemoglobin (OR＝0.01 ; P＝0.001) as significant factors inhibiting the introduction of cabazitaxel. Reducing the side effects of docetaxel, including early drug switching, may allow more CRPC patients to be reached with cabazitaxel. Consequently, the resulting taxane-based chemotherapy may contribute to an additional survival advantage.

Abstract PO5-01-05: An Open-label, Single-center Study Assessing the Efficacy of PH-based Regimen as Neoadjuvant Therapy for HER2-positive Early-stage Breast Cancer: Integrating Genomic Features and Functional Imaging

Abstract Background: Pathological complete response (pCR) has been demonstrated as a surrogate endpoint for disease-free and overall survival in HER2-positive early-stage breast cancer (EBC). Trastuzumab (H) plus pertuzumab (P) improved pCR rates in patients with HER2-positive early-stage breast cancer. Nevertheless, biomarkers to assess the effectiveness of this treatment in the neoadjuvant setting are still unclear. This study aims to evaluate the effectiveness of fluorodeoxyglucose positron emission tomography (18F-FDG-PET) and 68 Ga-Affibody HER2 Imaging PET (HER2-PET) in HER2 EBC neoadjuvant therapy, and to identify novel biomarkers for this regimen. Methods: HER2-positive EBC patients were prospectively recruited at Fudan University Shanghai Cancer Center between April 2020 and March 2022. All patients received the 1 dose of HP, followed by 6 cycles of docetaxel (T), carboplatin (Cb), and HP. We use FoundationOne to evaluate the genomic alterations before treatment. In addition, 18F-FDG-PET and HER2 PET were performed at baseline, after 1 cycle of HP, and after 6 cycles of TCbHP, to assess the effectiveness of these examinations in the prediction of pCR and correlation to disease burden. All patients were received surgery and completed 1 year of HP-based regimen in the adjuvant setting. Results: A total of 61 patients with a median age of 49 years were included. Among them, 93.5% of patients are node positive. 75.8% of the patients reported adverse events (AEs), primarily grade 1 and 2. The incidence of serious AEs was 6.6%. Patients exhibiting a greater than 40% reduction in SUVmax of 18-FDG-PET or HER2-PET scans from baseline to the fifth day after the initial HP treatment were classified as the treatment-sensitive group. The pCR rate for the 18-FDG-PET-sensitive group was 79.3%, while for the insensitive group was 48.1%. For HER2-PET scans, the pCR rate was 70.0% in the sensitive group and 59.3% in the non-sensitive group. To evaluate the potential biomarkers, 25 patients (13 pCR and 12 non-pCR) were evaluated with FoundationOne, with the identification of 1,321 somatic alterations. The most frequently altered genes were ERBB2 (100%), TP53 (96%), CDK12 (76%), MYC (56%), CCND1 (44%), PIK3CA (40%), and SRSF2 (36%). In the pCR group, we found PPM1D (38.5%) and RAD21 (38.5%) were altered more frequently than the non-pCR group. PIK3CA alterations were significantly reduced in pCR group, only 23% of cases are affected compared to 58.3% in non-pCR group. Patients were non-pCR had more MDM4 (41.7%) and ZNF217 (41.7%) alterations than pCR patients. Conclusion: The SUVmax value of 18-FDG-PET and HER2-PET scans are correlated well with the tumor burden and the residual disease in the HER2 EBCs. The reduction of SUVmax could predict pCR but need further exploration. Patients with alterations in PPM1D and RAD21 have a favorable response to the TCbHP regimen. Conversely, alterations in PIK3CA, MDM4, and ZNF217 are associated with treatment resistance. These results indicate the significance of 18-FDG-PET and HER2-PET in monitoring treatment effectiveness. The biomarker analysis in this study will help us understand the mechanism of HER2 positive breast cancer treatment resistance and assisting in tailoring personalized therapy. Clinical trial information: NCT04281641. Citation Format: Ming Chen, Benlong Yang, Sun Yuyun, Linxiaoxi Ma, Song Shaoli, Min He, Zhi-Ming Shao, Bingqiu Xiu, Jiong Wu. An Open-label, Single-center Study Assessing the Efficacy of PH-based Regimen as Neoadjuvant Therapy for HER2-positive Early-stage Breast Cancer: Integrating Genomic Features and Functional Imaging [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 PO5-01-05.

Abstract PO4-02-11: Optimizing Taxane-based Chemotherapy in Breast Cancer: Retrospective study comparing 4 cycles of TC to 6 cycles of TC

Abstract Breast cancer remains one of the most prevalent cancers among women worldwide. First-line chemotherapy options include anthracycline (AC-T) and Taxane (TC) based regimens. While anthracycline-based chemotherapy is most commonly used, the use of anthracycline-sparing regimens is also approved. The US Oncology 9735 trial conducted in the mid 2000s showed that four cycles of docetaxel and cyclophosphamide (TC4) were superior to four cycles of Doxorubicin and cyclophosphamide (AC). The follow-up ABC trials compared six cycles of TC(TC6) to AC-T. This trial showed that while AC-T was superior to TC, the difference was modest. AC-T has remained the standard of care, but TC is an acceptable option. One retrospective analysis involving 143 patients showed TC4 was non-inferior to TC6, and suggested that TC4 had fewer adverse events; however, statistical significance was not reached. The question remains whether six cycles of TC is required, or if four cycles is adequate. Methods: Patient information was retrieved from the EMR of a large private oncology group. The EMR was screened for all breast cancer patients who began treatment with TC between 1/1/2011 and 12/31/2021. Patients were required to have continuous follow-up, documented up to at least 6/30/2022. Only patients receiving TC as the first-line setting were included, while patients with metastatic disease were excluded. Adjusted Kaplan Meier curves for overall survival (OS) and disease-free survival (DFS) were generated. A log-rank test was used to determine the statistical difference between the two curves. OS was defined from the date of the last chemotherapy given to death. DFS is defined from the date of the last chemotherapy given to disease recurrence. The Chi-square analysis test of homogeneity was conducted to evaluate the differences in reported symptoms. Statistical analysis was completed with IBM SPSS version 29. Ethical approval was obtained from The Brooklyn Hospital Center Institutional Review Board. Results: A total of 376 charts were reviewed, out of which 224 met the criteria for inclusion. Of these 191 patients received TC4 and 33 received TC6. TC4 patients were noted to be older than TC6 patients. There were a higher percentage of hormone-positive cancers in the TC4 group while the TC6 group had a larger proportion of triple-negative breast cancers. There was a larger proportion of stage III patients that received TC6 than in TC4. TC6 patients were also noted to receive neo-adjuvant chemotherapy at a substantially higher rate. A greater proportion of patients in the TC4 group received breast-conserving surgery, with radiation than the TC6 group. TC6 had a completion rate of 76 % (Table 1). There was a significant difference in DFS noted between TC4 and TC6 (p = 0.016) with TC6 patients having a higher rate of relapse. No difference was noted in the overall survival. No differences were seen in side effects between TC4 and TC6, however, there was a trend toward high rates of neutropenia, anemia, and neuropathy seen in the TC6 group (Table 2). Conclusions: This real-world retrospective study reviewed patients who received TC in a large community oncology practice. The study reaffirms conclusions seen in previous retrospective studies conducted in the academic setting that there is no difference in overall survival when using six cycles of TC compared to four cycles of TC. Slight detriment was seen in the DFS setting when using TC6 however the small sample size along with the larger proportion of patients with stage III disease make it challenging to interpret this finding. There was a trend towards higher toxicities with TC6 that did not reach significance. Until a prospective randomized study comparing four vs six cycles of TC is conducted no definitive conclusions can be drawn, however, this study contributes to the current body of evidence that four cycles of TC is adequate and could potentially improve the quality of life of patients with early breast cancer. Table. Patient characteristics Patient characteristics including age, hormone status, stage, type of surgery, radiation, and treatment setting. Table. Adverse effects Adverse effect information obtained from physician documentation, and CBC reports documented at time of treatment with TC. Citation Format: Amith Ahluwalia, Michelle Koifman, Jaspreet Nannar, Bhavya Vachhani, Kanwal Ashraf, Maxim Shulimovich. Optimizing Taxane-based Chemotherapy in Breast Cancer: Retrospective study comparing 4 cycles of TC to 6 cycles of TC [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 PO4-02-11.

Abstract PO2-11-06: Anti-Müllerian hormone in Young women with breast CAncer to predict permanent loss of ovarian function after chemotherapy and anti-HER2 therapy (AMYCA): a biomarker analysis of the BETH and KAITLIN trials

Abstract Background: The ability to predict and identify ovarian function loss accurately after anticancer treatment is important for appropriate oncofertility counseling and to aid in therapy decision making for young women with early breast cancer (eBC). Anti-Müllerian hormone (AMH) has been proposed as both a pre- and post-treatment predictor of subsequent permanent loss of ovarian function. The present biomarker analysis conducted within two randomized controlled trials (RCTs) in a large and well-characterized patient population with HER2+ eBC receiving homogeneous treatment aimed to assess AMH use, alone and in combination with other hormonal biomarkers, for predicting loss of ovarian function at 36 months from randomization, i.e. approximately 2 years after end of therapy. Methods: BETH (NCT00625898) and KAITLIN (NCT01966471) were RCTs investigating adjuvant chemotherapy (CT) plus anti-HER2 therapy in high-risk HER2+ eBC patients. For the purpose of the present analysis, only samples of patients receiving currently adopted treatments were used, i.e. cohort 1A (6 cycles of docetaxel/carboplatin+trastuzumab (T)) and cohort 2A (3 cycles of docetaxel plus T followed by 3 cycles of anthracycline- and cyclophosphamide-based CT) of BETH trial, and arm 1 (3-4 cycles of anthracycline- and cyclophosphamide-based CT followed by 3-4 cycles of taxane plus T plus pertuzumab (P)) of KAITLIN trial. Women selected for this analysis were ≤45 years with known premenopausal status, available serum samples at baseline (pre-treatment) and/or end of therapy and 36 months (± 6 months) from randomization (i.e. min of 2 samples in all cases). Selected samples were centrally tested measuring AMH, follicle stimulating hormone (FSH) and estradiol (E2) using Roche Elecsys assays. Permanent ovarian loss was defined as FSH &amp;gt;25 IU/L and E2 &amp;lt; 110 pmol/L at 36 months. Results: Of 194 included patients, 62 were from BETH and 132 from KAITLIN. 139 (71.6%) received both taxane and anthracycline- and cyclophosphamide-based CT and 55 (28.4%) taxane only. Pertuzumab was used in addition to trastuzumab in 132 (68.0%) patients. AMH values declined from baseline median 8.44 pmol/L to undetectable levels in many women at end of therapy (median 0.08 pmol/L), with partial recovery at 36 months (median 0.14 pmol/L). Ovarian loss at 3 years was observed in 56 women with AMH available at baseline (29.5%) and in 52 women with AMH available at end of therapy (29.7%). For prediction of ovarian loss, in ROC analysis, AMH measured at baseline showed AUC 0.784 (internally validated using bootstrap: 0.783). While age influenced risk of ovarian loss, addition to AMH only slightly improved AUC to 0.800 (internal validation: 0.795) while addition of baseline FSH and E2 did not improve prediction. AMH measured at the end of therapy showed AUC 0.741 (internal validation: 0.742), which increased slightly to 0.785(internal validation: 0.781) with addition of age but without improved prediction with the addition of FSH and E2. The combination of AMH at baseline and end of therapy increased prediction slightly to 0.808 (internal validation 0.806) and with addition of age added to 0.820 (internal validation: 0.806). Conclusions: These results support the use of pretreatment measurement of AMH in predicting loss of ovarian function in women withHER2+ eBC aged ≤45 receiving CT and anti-HER2 therapy. Measurement of AMH at end of treatment was comparably valuable to pretreatment and added slightly to the value of pretreatment sampling. Inclusion of ovarian function assessment by measuring AMH before commencing treatment can inform subsequent risk of ovarian function loss with value for fertility preservation counselling and treatment decisions. Further validation is required in larger cohorts. Citation Format: Matteo Lambertini, Deirdre Allegranza, Ruediger Laubender, Nadia Harbeck, Sandra Swain, Charles Geyer, Dennis Slamon, Gabriella Bobba, Chiara Lambertini, Sanne Lysbet De Haas, Eleonora Restuccia, Ines Vaz Luis, David Cameron, Ian Krop, Eric Winer, Richard Anderson. Anti-Müllerian hormone in Young women with breast CAncer to predict permanent loss of ovarian function after chemotherapy and anti-HER2 therapy (AMYCA): a biomarker analysis of the BETH and KAITLIN 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 PO2-11-06.

Abstract PO4-01-03: Dual anti-HER2 Therapy with Pertuzumab and Trastuzumab versus Trastuzumab Alone in Addition to Anthracycline and Taxane-Based Neoadjuvant Therapy in Patients with HER2-Positive Early-Stage Breast Cancer; Real-World Data

Abstract Background: When use in the neoadjuvant setting, anti-HER2 targeted therapy had improved pathologic complete response rate (pCR) in patients with HER2-positive early-stage breast cancer (EBC). Here we present real-world data on the use trastuzumab with or without pertuzumab on the backbone of anthracycline and taxanes-based NSAPB-B27 chemotherapy regimen. Methods: We retrospectively reviewed records of patients with HER2-positive EBC who received neoadjuvant therapy using the National Surgical Adjuvant Breast and Bowel Project (NSABP)-B27 protocol (4 cycles of adriamycin and cyclophosphamide, followed by 4 more cycles of docetaxel; all given every 3 weeks) with anti-HER2 therapy from Jan 2014 to September 2021, treated at a tertiary care cancer center. The clinicopathological features, treatment received, and outcome were collected from patients’ electronic medical records. We estimated 3-year disease-free survival (DFS), a validated endpoint in HER2-positive EBC, using Kaplan-Meier with recurrence and/or death as events. Outcomes were reported in subgroups based on known prognostic factors. Results: The study comprised 528 patients with a median follow-up of 36 months. Median age was 48 (21-80) years. Hormone receptors (HR) were positive in 379 (71.8%), lymph node-involvement prior to neoadjuvant therapy was reported in 402 (76.1%) patients and 319 (60,4%) had grade-3 disease. Majority (n= 482, 91.3%) were labeled HER2-positive based on immunohistochemistry staining (IHC+3) and the rest were based on IHC+2 with positive FISH/ISH. Dual anti-HER2 therapy (trastuzumab and pertuzumab) was used in 316 (59.8%) patients, single agent trastuzumab in 173 (32.8 %) patients, while 39 (7.4%) others did not receive any anti-HER2 therapy. Except for 9 (1.7%) patients who progressed while on treatment, all patients underwent surgery. Among the whole group, 225 (43.4%) achieved pCR; significantly higher (n=80, 53.7%) in HR-negative compared to 38.3% among those with HR-positive disease, p=0.002. Additionally, pCR was higher in patients who received dual anti-HER2 (46.2%) compared to 39.3% for those treated with trastuzumab and 28.2% for those who did not receive anti-HER2 therapy. Following surgery, 463 (89.4%) of the patients received adjuvant trastuzumab, however, none of them received pertuzumab or TDM1 in adjuvant sitting. Estimated 3-year DFS was 86.1% with dual anti-HER2 and 83.0% with trastuzumab alone, p=0.19. However, DFS was better among those with node-negative disease; 96.5% compared to 80.9% in node-positive disease, p= &amp;lt; 0.001. Patients who achieved pCR had significantly better 3-year DFS; 89.3% compared to 80.2% in patients with residual disease, p= 0.006. Conclusions: Even with the wide use of pertuzumab in the neoadjuvant setting, the DFS was not improved compared to trastuzumab alone, and this highlights the importance of switching trastuzumab to TDM1, or to continue with pertuzumab in the adjuvant setting in patient with residual disease. Citation Format: Baha' Sharaf, Faris Tamimi, Osama Salama, Anas Zayed, Osama El Khatib, Suhaib Khater, Malek Horani, Suhaib Al-Sawajneh, Yosra AL-Masri, Hikmat Abdel-Razeq. Dual anti-HER2 Therapy with Pertuzumab and Trastuzumab versus Trastuzumab Alone in Addition to Anthracycline and Taxane-Based Neoadjuvant Therapy in Patients with HER2-Positive Early-Stage Breast Cancer; Real-World Data [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 PO4-01-03.

Abstract PS16-07: Tumor infiltrating lymphocyte stratification refines AJCC TNM staging based outcomes of early-stage triple negative breast cancer treated with neoadjuvant anthracycline-free, docetaxel and carboplatin chemotherapy

Abstract Background: Stromal tumor-infiltrating lymphocytes (sTILs) quantification is associated with pathological response to neoadjuvant chemotherapy (NAC) and long term outcomes in setting of adjuvant anthracycline based chemotherapy. A previous study in TNBC patients treated with adjuvant anthracycline chemotherapy shows that at a cut point of 30%, sTILs can up and downstage traditional AJCC stage groups. Additive impact of sTILs on refining outcomes beyond pathological response and TNM stage for patients treated with anthracycline-free chemotherapy is not known. This study aimed to investigate impact of sTILs on outcomes in a large cohort of TNBC patients treated with Docetaxel plus carboplatin NAC. Methods: Patients with stage I (T size &amp;gt; 1cm) to III TNBC scheduled to receive 6 cycles of NAC docetaxel (75 mg/m2) plus carboplatin (AUC 6) (TCb) every 3 weeks from two studies (NCT01560663 and NCT02302742) were combined for this analysis. sTILs were evaluated on pre-treatment H&amp;E slide using standard criteria centrally by one of the investigators (RS). Pathological complete response (pCR) was defined as ypT0/is ypN0. Logistic regression analysis was used to examine the effect of multiple variables on Event free survival (EFS) and overall survival (OS). Results: For 474 patients included in this analysis, median age was 52 years, 8% were Black, 13% had germline BRCA1/2 mutation, 44% had clinical Lymph node (LN) positive disease and 13%, 62% and 25% respectively had TNM stage I, II and III disease. Median sTILs were 5% (range 1-95%) and 25% had &amp;gt;30% sTILs. pCR and RCB 0+1 rates were 50.2% and 60.4% respectively. On multivariable analysis, T stage (OR=0.51, p=0.030), nodal status (OR=0.56, p=0.028), Ki67 (OR=2.74, p&amp;lt; 0.001) and sTILs (OR=2.01, p=0.014) were associated with pCR. pCR rate in those with sTILs &amp;lt; 30 vs sTILs &amp;gt;30 was 45.9% and 63.9% respectively (p=0.0014). At median follow-up of 58 months, 5 years EFS was 81.05% in all patients, 93.94% in those with pCR and 68.67% in those without pCR, 5 year OS was 84.83% in all patients, 96.53% in those with pCR and 74.13% in those with residual disease. On multivariate analysis lower T stage, negative LN status and increasing sTILS were associated with better EFS (T stage: HR =1.98, p=0.018; LN status: HR=2.92, p&amp;lt; 0.001; sTILs: HR:0.46, p=0.04) and OS (T stage: HR=1.89, p=0.040; LN status: HR=3.13, p=0.001; sTILs: HR=0.30, p=0.008). At a cut-point of 30%, sTILs up and downstaged anatomic AJCC TNM stage groups (table 1). Conclusions and Relevance: In patients treated with anthracycline-free TCb chemotherapy, sTILs were independent predictors of EFS and OS beyond clinicopathological features. Notably, 30% sTILs cut-point stratified outcomes beyond anatomical TNM staging. These, findings can aid in patient stratification for chemotherapy backbone de-escalation in future trials and have the potential to inform patient selection for adjuvant treatment escalation and de-escalation trials. Tumor infiltrating lymphocyte stratification refines AJCC TNM staging based outcomes of early-stage triple negative breast cancer treated with neoadjuvant anthracycline-free, docetaxel and carboplatin chemotherapy. Table. Citation Format: Miguel Martín, Rachel Yoder, Roberto Salgado, María del Monte-Millán, Enrique Álvarez, Isabel Echavarria, Joshua Staley, Coralia Bueno-Muiño, Yolanda Jerez Gilarranz, Andrew Godwin, María Cebollero, Oscar Bueno, José Ángel García-Sáenz, Fernando Moreno Antón, Uriel Bohn, Henry L Gómez, Tatiana Massarrah, Sara López-Tarruella, Priyanka Sharma. Tumor infiltrating lymphocyte stratification refines AJCC TNM staging based outcomes of early-stage triple negative breast cancer treated with neoadjuvant anthracycline-free, docetaxel and carboplatin chemotherapy [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 PS16-07.

Abstract PO5-02-14: Clinical-pathological determinant factors to choose between four or six cycles of adjuvant chemotherapy with docetaxel/cyclophosphamide (TC) in a retrospective real-world cohort of HER2-negative breast cancer patients

Abstract Introduction: The long-term severe adverse events associated with anthracyclines, including irreversible cardiotoxicity, myelodysplastic syndromes, and therapy-related leukemias, led researchers to question the risk-benefit of anthracycline-based chemotherapy regimens, especially for patients without axillary lymph node involvement, leading to an increasing trend to omit anthracyclines in adjuvant treatment. Docetaxel plus cyclophosphamide (TC) has replaced doxorubicin plus cyclophosphamide (AC) for lower-risk patients that need adjuvant chemotherapy. However, the optimal number of cycles of adjuvant in patients with node-positive or node-negative breast cancer is currently unknown. Methods: We performed a retrospective cohort study of patients with HER2-negative breast cancer, stage I to III, that received adjuvant docetaxel and cyclophosphamide (TC) for four or six cycles, treated from January 2010 to December 2021. Patients were included from four cancer institutions, both private and public, located in the South, Southeast, and Northeast of Brazil. Objectives: To investigate the clinical-pathological characteristics and survival of earlystage HER2-negative breast cancer patients who received four (TC4) or six cycles (TC6) of adjuvant docetaxel and cyclophosphamide (TC). Results: We collected data from six hundred and ninety-eight patients, 98.7% were female with an average age of 52 years, 51.9% were postmenopausal, 14.6% BRCA gene mutation, 66% had some comorbidity, and only 8.4% were not candidates for anthracyclines. Two hundred and twenty-five patients had public and 473 private health insurance. About 13.2% of the patients were hormone receptor negative (HR-) and 86.8% hormone receptor positive (HR+), 57.4% breast-conserving surgery and 77.7% sentinel lymph node (SL). Five hundred sixty-four (80.8%) patients received TC4 and 134 (19.2%) TC6. We observed that patients who received TC 6 had unfavorable prognostic factors such as: (TC4 vs TC6) previous breast cancer (8.7% vs 16.3%) (p=0.002), invasive ductal carcinoma (IDC) (73.4 vs 86.7%) (p=0.009), histological grade 3 (HG3) (34.9 vs 42.9%) (p= 0,085) conservative surgery (59.4% vs 53%) (p=0144), SL (80.9% vs 62.2%) (p =0.001), Lymph node positive (15% vs 42.3%) (p=0.001), pathological stage II (37.5% vs 50%) (p=0.001).Treatment completion rates were 96.5% and 84.3% for TC4 and TC6, respectively (p=0,02). The incidence of grade 3 or higher toxicity with TC6 (14% vs 21.1%; p= 0,043). Febrile neutropenia was observed in 6.7% of both groups. Grade 3 or higher neuropathy was most common with TC6 (2.2% vs 10.3%; p=0,163). Permanent treatment discontinuation was more frequent in the TC6 group (3.4% vs. 9.8%; p=0,004), as well as late toxicity (3.4% vs. 9.2%; p=0,004). Ninety-four percent of the patients completed the proposed cycles of chemotherapy, 72% received adjuvant radiotherapy and 85.4% received adjuvant hormone therapy, with 42% of these receiving an aromatase inhibitor for 5 years. The median follow-up of the entire cohort was 61 months. There was no difference in the 5-year DFS (77.5% vs. 64.7%; p=0.159) or the 5-year OS (89.5% vs. 70.5%; p= 0,06) between patients treated with TC4 and TC6. Conclusion: TC6 was commonly used for patients with unfavorable prognostic factors as history of previous breast cancer, (IDC), HG III, lymph node positive and stage II. Patients who received TC6 had less chance of completing the treatment and more severe toxicity, especially late peripheral neuropathy. There was no difference in DFS or OS. Citation Format: Mila Kraychete, Marcelle Cesca, Guilherme Almeida, Leonardo Santana, Luciana Leite, Solange M. Sanches, Vladmir Cordeiro de Lima, Rafaela Pirolli, Rafael Manea, Felipe Kaneta, Jean Coutinho, Lucas Vian, Waires Zeviani, Marcio Reis, Luciana Landeiro, Clarissa Mathias, Geila Nunez, Tamara Santana, Monique Tavares. Clinical-pathological determinant factors to choose between four or six cycles of adjuvant chemotherapy with docetaxel/cyclophosphamide (TC) in a retrospective real-world cohort of HER2-negative breast cancer patients [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 PO5-02-14.