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
Study Details
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.
Key Findings
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.
