Triple-negative breast cancer (TNBC) has a poor prognosis, and neoadjuvant chemotherapy (NACT) is the standard treatment for locally advanced TNBC. In this study, we aimed to evaluate the efficacy of adding carboplatin to NACT regarding pathological complete response (pCR) and survival in the HER2-low and HER2-zero subgroups of TNBC patients. The study included 269 patients from five medical oncology clinics. Patients were divided into two groups: HER2-low (n = 152, 56.5%) and HER2-zero (n = 117, 43.5%). Among HER2-zero patients, 30 (25.6%) received carboplatin, while 38 (25.0%) HER2-low patients received carboplatin. The benefit of adding carboplatin to NACT regarding pCR and survival was assessed in both HER2-zero and HER2-low groups. When patients were evaluated according to HER2 status, the pCR rates were significantly higher in the HER2-zero group compared to the HER2-low group (45.2% versus 23.7%, p < 0.001). In the HER2-zero group, patients who received carboplatin had significantly higher pCR rates (63.3% versus 39.0%, p = 0.021). Similarly, in the HER2-low group, adding carboplatin significantly increased the pCR rates (36.8% versus 19.3%, p = 0.028). While carboplatin improved pCR rates in both HER2 subgroups, this benefit was not observed in patients with Grade 1 tumors, HER2 score 2-FISH negative tumors, or based on BRCA mutation status. Patients with pCR exhibited significantly prolonged DFS and OS (p = 0.002, p < 0.001, respectively). Our research demonstrates that the addition of carboplatin increases pCR rates in both HER2-zero and HER2-low patient cohorts. We suggest that carboplatin should be considered as an addition to standard neoadjuvant chemotherapy for eligible TNBC patients, regardless of HER2-zero or HER2-low status, when appropriate based on individual patient factors and toxicity considerations.

Background and Objectives: Perioperative fluorouracil, leucovorin, oxaliplatin, and docetaxel (FLOT) is the standard of care for resectable gastric and gastroesophageal junction adenocarcinoma; however, up to 50% of patients develop metastatic recurrence. These patients have prior exposure to platinum and taxane agents, and optimal first-line treatment in the metastatic setting remains undefined. This study aimed to characterize real-world treatment patterns and outcomes in patients progressing after perioperative FLOT, focusing on relapse timing and HER2 status. Materials and Methods: This retrospective, multicenter cohort study included 296 patients from 31 centers across Türkiye, stratified into early relapse (≤6 months, n = 114) and late relapse (>6 months, n = 182) groups. Survival analyses were performed using the Kaplan-Meier method and Cox proportional hazards regression. Primary endpoints were progression-free survival (PFS) and overall survival (OS). Results: Median PFS and OS for the entire cohort were 6 and 9 months, respectively. Early relapsers had significantly shorter median PFS (4 vs. 6 months, p = 0.029) and OS (8 vs. 12 months, p = 0.047); however, early relapse timing did not retain independent prognostic significance on multivariable analysis. No significant difference in PFS or OS was observed between cytotoxic chemotherapy regimens in either relapse group. HER2 positivity was the only independent predictor of improved PFS on multivariable Cox analysis (HR 0.48, 95% CI 0.29–0.81; p = 0.006). In the late relapse group, trastuzumab-based chemotherapy achieved a median PFS of 14 months and OS of 18 months, significantly superior to all cytotoxic regimens (PFS p = 0.007; OS p = 0.029). Conclusions: In patients progressing after perioperative FLOT, cytotoxic chemotherapy regimen selection did not demonstrate a statistically significant survival difference in this retrospective cohort, regardless of relapse timing. HER2 positivity is the dominant predictive biomarker, and trastuzumab-based therapy suggests a potential survival benefit that warrants prospective validation. Comprehensive biomarker profiling at metastatic diagnosis and prospective trials designed for this post-FLOT population are needed to establish evidence-based treatment standards.

Background: Adenocarcinoma arising from the ampulla of Vater is an extremely rare neoplasm, and there are limited data regarding frontline therapy for metastatic disease. We investigated the outcomes of first-line treatment with FOLFIRINOX by comparing it with other treatments in patients with advanced ampullary adenocarcinoma. Methods: We included 123 patients with advanced ampullary adenocarcinoma who were treated with frontline FOLFIRINOX (n = 32), fluorouracil (FU)-based chemotherapy (n = 20), and gemcitabine-based chemotherapy (n = 65) between August 2007 and January 2024 in this retrospective study. The median progression-free survival (mPFS) and overall survival (mOS) according to treatment and clinicopathological features were calculated using the Kaplan–Meier method. Results: The median age of the patients was 62 years (range, 36–78), and 75,6% of the patients had an ECOG performance status of 0–1. The mOS were 13 months (95% CI, 10.6–14.4), 11 months (95% CI, 10.6–14.4), and 12 months (95% CI, 10.6–14.4), respectively [p = 0.865]. There were no significant differences in OS among the chemotherapeutic agents according to histological subtypes. However, FOLFIRINOX and FU-based treatments appeared more effective in the intestinal subtype, while gemcitabine-based therapies were less effective. In the pancreaticobiliary subtype, FU-based therapies yielded a shorter outcome compared to FOLFIRINOX and gemcitabine-based therapies. Grade 3 or 4 hematologic toxicities were higher in patients treated with FOLFIRINOX. Conclusions: In advanced ampullary adenocarcinoma, despite higher toxicity, frontline FOLFIRINOX showed a trend toward an OS benefit in the intestinal subtype while providing a similar outcome in the pancreaticobiliary subtype.

The recommended adjuvant chemotherapy (adj‐ChT) regimen for resected biliary tract cancers (BTC) is capecitabine (Cape); yet, the recommendation is based on limited evidence. Although varied adj‐ChTs have been employed in practice, robust real‐world data is scarce. We conducted a national, multicenter, hospital‐based registry study to evaluate adj‐ChTs in resected BTCs. Patients who received adj‐ChT (± radiotherapy) between 2010 and 2024 were included. Recurrence‐free (RFS) and overall survival (OS) were analyzed by adjusted Cox‐regression and propensity score‐based inverse‐probability‐of‐treatment‐weighting (IPTW), addressing selection bias. Among 617 patients from 44 centers, 513 were eligible. The most frequent adj‐ChTs were Cape (35.5% [ n = 182]), gemcitabine–cisplatin (Gem‐Cis; 22.4% [ n = 115]), gemcitabine–capecitabine (Gem‐Cape; 20.1% [ n = 103]), and gemcitabine (Gem; 10.7% [ n = 55]). Median RFS and OS with Cape were 19.7 (95% Confidence Interval [95% CI]: 14.2–41.1) and 41.9 months (95% CI: 25.9–69.2). In adjusted/controlled comparisons with Cape, no differences in RFS or OS were observed with Gem‐Cis (RFS: Hazard Ratio [HR] 1.13 [95% CI: 0.77–1.66]; OS: HR: 1.03 [95% CI: 0.66–1.61]), Gem‐Cape (RFS: HR 0.97 [95% CI: 0.68–1.38]; OS: HR: 0.81 [95% CI: 0.52–1.24]), or Gem (RFS: HR 1.00 [95% CI: 0.63–1.59]; OS: HR: 0.93 [95% CI: 0.55–1.57]). Similarly, IPTW analyses showed no difference in RFS and OS. Radiotherapy appeared to be associated with improved survival. Performance status, T‐stage, lymph‐node positivity, and R1‐resection were independently associated with RFS and OS. In conclusion, this real‐world study did not identify a regimen superior to Cape. Given the modest benefit of adj‐ChTs, novel approaches, including neoadjuvant and targeted/immunotherapy strategies, are needed.

Background: Ampullary adenocarcinoma is a rare cancer for which there are no standard adjuvant treatment recommendations due to the lack of randomized clinical trials. The primary aim of this analysis is to investigate the efficacy of adjuvant FOLFIRINOX treatment in patients with resected ampullary adenocarcinoma. Materials and Methods: This multicenter retrospective cohort study was conducted at 15 institutions in Turkey between August 2007 and January 2024, involving 211 patients with resected, non-metastatic ampullary adenocarcinoma receiving adjuvant chemotherapy with various chemotherapy regimens with or without chemoradiation. Clinicopathological and treatment-related parameters were recorded. Disease-free survival (DFS) and overall survival (OS) were analyzed by using Kaplan–Meier estimates. Cox proportional hazards regression was used to identify covariates associated with OS. Results: The median follow-up time was 52 months, and 116 patients (55.2%) were alive at the time of the analysis. The median age was 61 years (32–82). mFOLFIRINOX was administered to 16.6% of the patients (n = 35). The 3-year DFS rate was 79.41% in the FOLFIRINOX-treated arm and 53.9% in the other treatment arm (p = 0.034 for mDFS). The median OS was non-reached in patients receiving mFOLFIRINOX treatment, while it was 51 months in patients receiving other treatments (p = 0.071). While no statistically significant results were reached, a trend toward statistically significant survival times was observed in the FOLFIRINOX arm. After adjustment for other prognostic parameters, mFOLFIRINOX remained an independent statistically significant parameter for better OS (HR; 95% CI: 3.24; 1.02–10.9; p = 0.046). Conclusions: FOLFIRINOX treatment has shown efficacy in the adjuvant treatment of ampullary cancer, independent of histological subtype. The findings should be validated in large prospective trials.