1. Docetaxel-oxaliplatin-capecitabine/5-fluorouracil (DOX/F) followed by docetaxel versus oxaliplatin-capecitabine/5-fluorouracil (CAPOX/FOLFOX) in HER2-negative advanced gastric cancers.
- Author
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Ramaswamy A, Bhargava P, Dubashi B, Gupta A, Kapoor A, Srinivas S, Shetty O, Jadhav P, Desai V, Noronha V, Joshi A, Menon N, Patil VM, Mishra BK, Sansar B, Singh A, Patel S, Singh SN, Dhal I, Vinayak KR, Pal V, Mandavkar S, Kannan S, Chaugule D, Patil R, Parulekar M, Nashikkar C, Ankathi SK, Kaushal RK, Shah A, Ganesan P, Kayal S, Ananthakrishnan R, Syed N, Samaddar D, Kapu V, Shah A, Kaaviya D, Suganiya R, Srinivasan ND, Prabhash K, and Ostwal V
- Subjects
- Humans, Middle Aged, Female, Male, Aged, Adult, Kaplan-Meier Estimate, Organoplatinum Compounds administration & dosage, Microsatellite Instability, Esophageal Neoplasms drug therapy, Esophageal Neoplasms genetics, Esophageal Neoplasms mortality, Esophageal Neoplasms pathology, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Antineoplastic Combined Chemotherapy Protocols adverse effects, Stomach Neoplasms drug therapy, Stomach Neoplasms genetics, Stomach Neoplasms mortality, Fluorouracil administration & dosage, Fluorouracil adverse effects, Capecitabine administration & dosage, Capecitabine adverse effects, Docetaxel administration & dosage, Leucovorin administration & dosage, Leucovorin adverse effects, Receptor, ErbB-2 genetics, Oxaliplatin administration & dosage, Adenocarcinoma drug therapy, Adenocarcinoma genetics, Adenocarcinoma mortality, Esophagogastric Junction
- Abstract
Background: We evaluated whether the addition of docetaxel (D) to a combination comprising 5-fluorouracil/leucovorin (5-FU/LV) or capecitabine (C) plus oxaliplatin (O) (DOF/DOX) improved overall survival (OS) compared with 6 months of 5-fluorouracil (5-FU) or capecitabine in combination with oxaliplatin (FOLFOX/CAPOX) alone in advanced HER2-negative gastroesophageal junction and gastric adenocarcinomas (G/GEJ)., Methods: This study was an investigator-initiated, open-label, multi-institutional, randomized phase III trial in adult patients with HER2-negative advanced G/GEJs. The primary endpoint of the study was a comparison of median OS by Kaplan-Meier method. Next-generation sequencing was performed on tissue., Results: Of the 324 patients randomly assigned between July 2020 and November 2022, 305 patients were evaluable for analysis (FOLFOX/CAPOX: 156; DOF/DOX: 149). With a median follow-up time of 19.2 months (95% Confidence Interval [CI] = 16.5 months to 21.9 months) for the entire cohort, the median OS was 10.1 months (95% CI = 9.2 to 10.9) for FOLFOX/CAPOX and 8.9 months (95% CI = 7.3 to 10.5) for DOF/DOX, and this difference was not statistically significant (P = .70). An increased proportion of grade 3 or grade 4 neutropenia (21% vs 3%; P < .001) and grade 2/3 neuropathy (17% vs 7%; P = .005) was seen in patients receiving DOF/DOX. Genomic profiling revealed a low incidence of microsatellite instability (1%) and a high incidence of BRCA1 (8.4%) and BRCA2 (7.5%) somatic alterations., Conclusion: FOLFOX or CAPOX chemotherapy for 6 months remains one of the standards of care in advanced HER2-negative gastroesophageal junction and gastric adenocarcinomas, with no additional survival benefit seen with the addition of docetaxel. Genomic profiling of patients revealed a higher than previously known incidence of somatic BRCA alterations, which requires further evaluation.CTRI (Clinical Trial Registry of India: CTRI/2020/03/023944)., (© The Author(s) 2024. Published by Oxford University Press.)
- Published
- 2024
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