Second-line avelumab works against dMMR/MSI metastatic colorectal cancer

Treatment with the immune checkpoint inhibitor avelumab in the second-line setting confers survival and disease control benefits in patients with deficient mismatch repair and/or microsatellite instability (dMMR/MSI) metastatic colorectal cancer (mCRC) when compared with standard treatment, with a favourable safety profile, according to the results of the phase II SAMCO-PRODIGE 54 trial.

SAMCO-PRODIGE 54 included 122 patients (median age 66 years, 53.3 percent women, 82.0 percent had right-sided tumour, 42.6 percent had BRAF V600E–mutated tumours) with dMMR/MSI mCRC who experienced progression while on standard first-line therapy. These patients were randomly assigned to receive standard second-line therapy or avelumab every 2 weeks until progression, unacceptable toxic effects, or patient refusal. Patient and tumour characteristics at baseline were between treatment groups.

After a median follow-up of 33.3 months, avelumab performed better than chemotherapy with or without targeted agents with respect to the primary endpoint of progression-free survival PFS according to RECIST (Response Evaluation Criteria in Solid Tumours). The proportion of patients without progression was 24.6 percent vs 8.2 percent (p=0.03).

PFS rates with avelumab vs standard treatment were 31.2 percent (95 percent confidence interval [CI], 20.1–42.9) vs 19.4 percent (95 percent CI, 10.6–30.2) at 12 months and 27.4 percent (95 percent CI, 16.8–39.0) vs 9.1 percent (95 percent CI, 3.2–18.8) at 18 months.

Objective response rates were similar in the two treatment groups (29.5 percent vs 26.2 percent; p=0.45).

Ongoing disease control at 18 months was documented in 18 patients (75.7 percent) in the avelumab group and in nine (19.1 percent) in the control group.

As for safety, no new concerns in either group were detected. Of note, fewer treatment-related adverse events of at least grade 3 were recorded in the avelumab group than in the control group (31.7 percent vs 53.1 percent; p=0.02).