Fluoropyrimidine+cisplatin/oxaliplatin+trastuzumab therapy is recommended for the first-line treatment of HER2-positive metastatic gastric adenocarcinoma. However, there is no comprehensive study on which platinum-based treatment should be preferred. This study aimed to compare the treatment response and survival characteristics of patients with HER2-positive metastatic gastric or gastroesophageal junction (GEJ) cancer who received fluorouracil, oxaliplatin, and leucovorin (mFOLFOX)+trastuzumab or cisplatin and fluorouracil (CF)+trastuzumab as first-line therapy. It was a multicenter, retrospective study of the Turkish Oncology Group, which included 243 patients from 21 oncology centers. There were 113 patients in the mFOLFOX+trastuzumab arm and 130 patients in the CF+trastuzumab arm. The median age was 62 years in the mFOLFOX+trastuzumab arm and 61 years in the CF+trastuzumab arm (P = 0.495). 81.4% of patients in the mFOLFOX+trastuzumab arm and 83.1% in the CF+trastuzumab arm had gastric tumor localization (P = 0.735). The median progression-free survival (PFS) was significantly higher in the mFOLFOX+trastuzumab arm (9.4 months vs. 7.3 months, P = 0.024). The median overall survival (OS) was similar in both groups (18.4 months vs. 15.1 months, P = 0.640). Maintenance trastuzumab was continued after chemotherapy in 101 patients. In this subgroup, the median OS was 23.3 months and the median PFS was 13.3 months. In conclusion, FOLFOX+trastuzumab is similar to CF+trastuzumab in terms of the median OS, but it is more effective in terms of the median PFS in the first-line treatment of HER2-positive metastatic gastric and GEJ cancer. The choice of treatment should be made by considering the prominent toxicity findings of the chemotherapy regimens.

Aim: Hormone receptor (HR)-positive, human epidermal growth factor 2 (HER2)-negative breast cancer which represents the most common subgroup of metastatic breast cancer (MBC). Recently, further subclassification for HER2-negative tumors has emerged as HER2-low. There is limited knowledge regarding the effect of HER2-low expression on outcomes of patients with HR-positive and HER2-negative MBC treated with CDK 4/6 inhibitors plus hormonal therapy. Therefore, we evaluated survival parameters according to HER2-low status for this patient group in this study. Material and Methods: As the Turkish Oncology Group (TOG) Project, retrospectively collected data from 423 patients with HR-positive/HER2-negative MBC treated with ribociclib and palbociclib plus letrozole therapy was assessed. Included patients had metastatic first-line therapy and endocrine-sensitive disease. Survival outcomes were compared between HER2-negative and HER2-low patient groups. Conclusion: HER2-low status had no statistically significant impact on survival in patients treated with palbociclib or ribociclib plus letrozole.

Germline BRCA1/2-mutated (gBRCAm) hormone receptor-positive/HER2-negative (HR+/HER2-) metastatic breast cancer (MBC) is a biologically distinct subset in which the efficacy of cyclin-dependent kinase 4/6 (CDK4/6) inhibitors remains incompletely characterized. We evaluated real-world outcomes and prognostic factors in a multicenter retrospective Turkish cohort treated with a CDK4/6 inhibitor plus endocrine therapy (June 2020–September 2025). Progression-free survival (PFS) and overall survival (OS) were estimated using Kaplan–Meier and Cox methods. Among 121 patients, 30 (24.8%) had BRCA1, 88 (72.7%) had BRCA2, and three (2.5%) had dual mutations; 66.9% received first-line therapy, with ribociclib in 69.4% and palbociclib in 29.8%. Objective response rate was 69.4% and the clinical benefit rate was 82.6%. Median PFS was 17.0 months and OS 47.0 months. PFS was numerically longer in BRCA1 than in BRCA2 carriers (25.0 vs. 14.0 months), although the difference was not statistically significant in the pairwise comparison (HR 1.50, 95% CI 0.88–2.56; log-rank p = 0.135); the dual BRCA1/2 subgroup (n = 3) had the poorest outcomes and was assessed descriptively. OS did not differ significantly between BRCA1 and BRCA2 carriers (57.0 vs. 49.0 months; log-rank p = 0.520). PFS did not differ between ribociclib and palbociclib (p = 0.192); OS favored ribociclib at borderline significance (p = 0.050), but this was not confirmed in Cox regression. In multivariable analysis, ECOG ≥ 1 (HR 1.85; p = 0.010) and fulvestrant-based therapy (HR 1.74; p = 0.041) predicted shorter PFS; fulvestrant also predicted worse OS (HR 2.39; p = 0.008). CDK4/6 inhibitor-based therapy shows meaningful activity in gBRCAm HR+/HER2- MBC; the numerically poorer outcomes observed in BRCA2 carriers are hypothesis-generating and warrant validation in larger cohorts.

E15587 Background: Expanded RAS analysis is essential for the selection of biologic agents in mCRC. RAS mutations indicates anti-EGFR unresponsiveness. In this study, we aimed to investigate RAS and BRAF mutations by liquid biopsy at progression in patients with RAS mutant mCRC. Methods: Sixty patients with mCRC who harbored tissue RAS mutations were prospectively analyzed between July 2019 and April 2020. All the patients treated with chemotherapy plus bevacizumab combinations . The plasma samples of the patients were analyzed after progression of bevacizumab combinations. RAS mutation profile was evaluated in plasma using Idylla PCR-based molecular diagnostics method, which enables rapid detection of common mutations in RAS and BRAF genes in circulating tumor DNA (ctDNA). Kaplan-Meier method was used for survival analysis and log-rank test was performed for comparison of groups. Results: The median age of the patients was 60 years (IQR:35-83 years) and female was (n=23, 38.3%). Primary tumor was located in the left colon in 81.7% of all patients. There were 95.0% KRAS and 5% NRAS mutations in baseline tissue biopsy. As a result of liquid biopsy after progression, 55.0% of the patients had KRAS, 3.3% NRAS and 3.3% had BRAF mutations. The RAS mutation detected in 58.3% of the patients. While there was no significant difference in terms of clinicopathological features between wild type (RAS/BRAF) and mutant type (RAS/BRAF) determined by liquid biopsy, the overall survival (OS) of the wild type group was significantly longer than mutant group (43.8 vs. 20.4 months, p= 0.002). Conclusions: This study demonstrated that there may be changes in RAS/BRAF mutation from plasma analysis after progression in patients with mCRC. Since better survival in the patient group with wild type was detected compared to the RAS concordance group, the evaluation of RAS mutation status at the time of progression may be important in terms of disease prognosis and treatment options.