Impact of sex and age on chemotherapy efficacy, toxicity and survival in localised oesophagogastric cancer: A pooled analysis of 3265 individual patient data from four large randomised trials (OE02, OE05, MAGIC and ST03)
- PMID: 32745964
- DOI: 10.1016/j.ejca.2020.06.005
Impact of sex and age on chemotherapy efficacy, toxicity and survival in localised oesophagogastric cancer: A pooled analysis of 3265 individual patient data from four large randomised trials (OE02, OE05, MAGIC and ST03)
Abstract
Background: There is a lack of large-scale randomised data evaluating the impact of sex and age in patients undergoing chemotherapy followed by potentially curative surgery for oesophagogastric cancer.
Patients and methods: Individual patient data from four prospective randomised controlled trials were pooled using a two-stage meta-analysis. For survival analysis, hazard ratios (HRs) were calculated for patients aged <70 and ≥ 70 years, as well as between males and females. Mandard tumour regression grade (TRG) and, ≥grade III toxicities were compared using logistic regression models to calculate odds ratios. All analyses were adjusted for the type of chemotherapy received.
Results: 3265 patients were included for survival analysis (2668 [82%] male, 597 [18%] female; 2627 (80%) <70 years, 638 (20%) ≥70 years). A significant improvement in overall survival (OS) (HR: 0.78; p < 0.001) and disease-specific survival (DSS) (HR: 0.78; p < 0.001) was observed in females compared with males. No significant differences in OS (HR: 1.11; p = 0.045) or DSS (HR: 1.01; p = 0.821) were observed in older patients compared with younger patients. For patients who underwent resection, older patients (15% vs 10%; p = 0.03) and female patients (14% vs 10%, p = 0.10) were more likely to achieve favourable Mandard TRG scores. Females experienced significantly more ≥grade III nausea (10% vs 5%; p≤0.001), vomiting (10% vs 4%; p≤0.001) and diarrhoea (9% vs 4%; p≤0.001) than males.
Conclusions: In this large pooled analysis using prospective randomised trial data, females had significantly improved survival while experiencing more gastrointestinal toxicities. Older patients achieved comparable survival to younger patients and thus, dependent on fitness, should be offered the same treatment paradigm.
Keywords: Age; Chemotherapy; Gastric cancer; Oesophageal cancer; Sex; Survival.
Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.
Conflict of interest statement
Conflict of interest statement D.C. reports receiving research funding from Amgen, Sanofi, Merrimack, AstraZeneca, Celgene, MedImmune, Bayer, 4SC, Clovis, Eli Lilly, Janssen, Merck; sits on the scientific advisory board for OVIBIO. R.E.L. reports serving an advisory role for Bayer; receiving research funding from Bayer. I.C. reports serving on the advisory board for Eli-Lilly, Bristol Meyers Squibb, MSD, Bayer, Roche, Merck-Serono, Five Prime Therapeutics, Astra-Zeneca, Oncologie International, and Pierre Fabre; has received research funding from Eli-Lilly, Janssen-Cilag, Sanofi Oncology, and Merck-Serono; has received an honorarium from Eli-Lilly. N.S. has received research funding from AstraZeneca, BMS, and Pfizer; has received honoraria from Eli Lilly, Merck Serono, MSD Oncology, and Pierre Fabre; has received travel grants from AstraZeneca, BMS, Eli Lilly, Merck, Roche; has served on the advisory board for Pfizer, AstraZeneca, and Servier. A.A., M.N., D.A., H.I.G. and W.A. declare no competing interests.
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