Impact of age on efficacy and early mortality of initial sequential treatment versus upfront combination chemotherapy in patients with metastatic colorectal cancer: a subgroup analysis of a phase III trial (AIO KRK0110, XELAVIRI study)
- PMID: 32750502
- DOI: 10.1016/j.ejca.2020.06.010
Impact of age on efficacy and early mortality of initial sequential treatment versus upfront combination chemotherapy in patients with metastatic colorectal cancer: a subgroup analysis of a phase III trial (AIO KRK0110, XELAVIRI study)
Abstract
Introduction: The XELAVIRI study compared application of fluoropyrimidine (FP) and bevacizumab (Bev) followed by sequential escalation to irinotecan (Iri), FP and Bev (arm A) to upfront combination therapy with FP, Iri and Bev (arm B) in patients with metastatic colorectal cancer (mCRC). To elucidate the impact of age on survival, we evaluated efficacy and early mortality in the underlying trial.
Methods: Patients were stratified for age in three cohorts (<65 years, 65-74 years and ≥75 years). Survival end-points were expressed by the Kaplan-Meier method and compared by log-rank testing and Cox regression. Objective response and 60-day mortality were evaluated by chi-square testing.
Results: The efficacy analyses suggest more substantial benefit from upfront combination chemotherapy in younger patients with mCRC. Elderly patients (≥75 years) derived limited benefit from upfront combination chemotherapy, particularly in terms of overall survival. Of 421 randomised patients, 13 patients (3.1%) died within 60 days after treatment initiation with the highest prevalence in elderly patients (1.6% < 65 years, 2.8% 65-74 years and 5.2% ≥ 75 years, p = 0.26). The frequency of 60-day mortality was significantly associated with age (with a maximum of 8.7% in patients aged ≥75 years) in patients undergoing upfront combination therapy (p = 0.027) but not in patients receiving sequential treatment (p = 0.63).
Conclusion: Combination therapy with FP, Iri and Bev does not substantially improve the outcome of patients aged ≥75 years as compared with sequential treatment algorithm. These patients appear to be at a relevant risk for 60-day mortality under Iri-based combination chemotherapy plus Bev.
Keywords: 60-day mortality; Bevacizumab; Combination chemotherapy; Early mortality; Irinotecan; Metastatic colorectal cancer.
Copyright © 2020 Elsevier Ltd. All rights reserved.
Conflict of interest statement
Conflict of interest statement A.K. reports receiving funds for travel, accommodations and expenses from Roche and Medac. V.H. reports receiving honoraria from Roche, Celgene, Amgen, Sanofi, Merck, Sirtex Medical, Baxalta, Eli Lilly, Boehringer Ingelheim, Taiho Pharmaceutical and Servier; serving a consulting or advisory role in Merck, Amgen, Roche, Sanofi, Boehringer Ingelheim, Celgene, Sirtex Medical, Baxalta, Servier, Halozyme, MSD and Bristol-Myers Squibb; receiving research funding from Merck (Inst), Amgen (Inst), Roche (Inst), Celgene (Inst), Boehringer Ingelheim (Inst), Sirtex Medical (Inst) and Shire (Inst) and receiving funds for travel, accommodations and expenses from Merck, Roche, Sirtex Medical, Amgen, Servier, Shire, MSD and Bristol-Myers Squibb. L.F.v.W. reports receiving honoraria from Novartis, Roche andSanofi and funds for travel, accommodations and expenses from Amgen. T.D. reports serving a consulting or advisory role in Novartis. C.D. reports serving a consulting or advisory role in Amgen, Roche and Janssen Pharmaceuticals and receiving funds for travel, accommodations and expenses from Celgene, Janssen Pharmaceuticals and Novartis. U.G. reports receiving honoraria from Servier, Boehringer Ingelheim, Sirtex Medical and Daiichi Sankyo; serving a consulting or advisory role in Novartis, Merck, Amgen, Hexal and Bristol-Myers Squibb and receiving funds for travel, accommodations and expenses from Merck and Amgen. I.S. reports receiving honoraria from Roche, AbbVie, Janssen Pharmaceuticals, Novartis and Servier; serving a consulting or advisory role in AbbVie, Janssen Pharmaceuticals, Novartis and Roche and receiving funds for travel, accommodations and expenses from AbbVie, Janssen Pharmaceuticals and Novartis. K.H. reports receiving honoraria from Roche and funding for travel, accommodations and expenses from Amgen, Celgene and Lilly. A.J. reports serving a consulting or advisory role in Boehringer Ingelheim, Roche, Biocartis, Bristol-Myers Squibb, Amgen, AstraZeneca, Thermo Fisher Scientific and Merck and being a member of the Speakers' Bureau for AstraZeneca, Roche, Bristol-Myers Squibb and Amgen. S.S. reports receiving honoraria from Merck, Roche, Amgen, Bayer, Sanofi, Sirtex Medical, Eli Lilly, Pierre-Fabre, Servier and Taiho; serving a consulting or advisory role in Merck, Roche, Sanofi, Bayer, Amgen, Boehringer Ingelheim, Eli Lilly, Takeda, MSD and Pierre-Fabre and receiving funds for travel, accommodations and expenses from Merck, Roche, Sanofi, Bayer, Sirtex Medical, Amgen, Eli Lilly, Takeda and Pierre-Fabre. C.G.-J. reports receiving funds for travel, accommodations and expenses from Roche. D.P.M. reports receiving honoraria from Merck Serono, Amgen, Roche, Servier, Bristol-Myers Squibb, Pfizer and Sirtex Medical; serving a consulting or advisory role in Merck Serono, Amgen and Bayer; receiving research funding from Merck Serono (Inst), Roche (Inst) and Amgen (Inst) and receiving funds for travel, accommodations and expenses from Amgen, Merck Serono, Bayer, Servier and Bristol-Myers Squibb. All other authors report no conflict of interest.
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