In the French phase II SAMCO-PRODIGE 54 trial reported in JAMA Oncology, Julien Taïeb, MD, PhD, and colleagues found that second-line avelumab improved progression-free survival vs standard chemotherapy in patients with mismatch repair–deficient and/or microsatellite instability (dMMR/MSI) metastatic colorectal cancer.
Julien Taïeb, MD, PhD
In the open-label multicenter trial, 122 patients (modified intent-to-treat [mITT] population) with disease progression on standard first-line therapy were randomly assigned between April 2018 and April 2021 to receive avelumab at 10 mg/kg every 2 weeks until disease progression or unacceptable toxicity (n = 61) or investigator’s choice of standard second-line chemotherapy with or without a targeted agent (n = 61). Chemotherapeutic options included modified FOLFOX6 (leucovorin, fluorouracil, oxaliplatin) with or without cetuximab and FOLFIRI (leucovorin, fluorouracil, irinotecan) with or without bevacizumab or cetuximab determined according to first-line treatment and RAS/BRAF status. The primary endpoint was investigator-assessed progression-free survival in the mITT population.
Median follow-up was 33.3 months (95% confidence interval [CI] = 28.3–34.8 months). Median progression-free survival was 4.1 months in the avelumab group vs 6.2 months in the control group. However, progression-free survival Kaplan-Meier curves crossed at 7.3 months; analysis showed that a greater proportion of patients in the avelumab group vs the control group remained free of events over follow-up (P = .03). Rates at 12 and 18 months were 31.2% (95% CI = 20.1%–42.9%) vs 19.4% (95% CI = 10.6%–30.2%) and 27.4% (95% CI = 16.8%–39.0%) vs 9.1% (95% CI = 3.2%–18.8%).
Objective response rate was 29.5% vs 26.2% (P = .45). Stable disease rate was 41.0% vs 50.8%, and disease control rate was 70.5% vs 77.0%. Among the 43 vs 47 patients with disease control, 18 (75.7%) in the avelumab group vs 9 (19.1%) in the control group had ongoing disease control at 18 months.
The authors noted that no new safety concerns were observed in either group. Grade ≥ 3 treatment-related adverse events occurred in 31.7% of patients in the avelumab group vs 53.1% in the control group (P = .02).
The investigators concluded: “The SAMCO-PRODIGE 54 phase II randomized clinical trial showed, in patients with dMMR/MSI metastatic colorectal cancer, better progression-free survival and disease control duration with avelumab over standard second-line treatment, with a favorable safety profile.”
Dr. Taïeb, of Hôpital Européen Georges Pompidou, Université Paris-Cité, is the corresponding author of the JAMA Oncology article.
Disclosure: The study was supported by Merck-KGaA and Fédération Francophone de Cancérologie Digestive. For full disclosures of the study authors, visit jamanetwork.com.The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.