Avelumab plus cetuximab versus cetuximab alone in metastatic colorectal cancer patients

This randomized phase II trial investigated the efficacy of combining avelumab with cetuximab versus cetuximab monotherapy in patients with metastatic colorectal cancer. The study population consisted of 156 randomly assigned patients, with 104 in arm A and 52 in arm B. The patients were specifically selected as RAS/BRAF wild-type. The setting location was not reported. The study followed participants for a median duration of 5.3 months.

The intervention involved administering cetuximab plus avelumab in arm A, while arm B received cetuximab monotherapy. Specific dosing protocols were not detailed in the provided data. The primary outcome measured was overall survival. Secondary outcomes included progression-free survival and objective response rate.

Regarding the primary outcome, median overall survival in arm A was 14.8 months with a 95% confidence interval of 12.1 to 18.3 months. In arm B, median overall survival was 12.9 months with a 95% confidence interval of 11 months to not evaluable. The hazard ratio was 1.00 with a 95% confidence interval of 0.65 to 1.52. The p-value was 0.983, indicating no statistically significant difference between the groups.

For the secondary outcome of progression-free survival, median progression-free survival in arm A was 5.3 months with a 95% confidence interval of 4.3 to 6 months. In arm B, median progression-free survival was 4.3 months with a 95% confidence interval of 3.5 to 5.5 months. The hazard ratio was 0.78 with a 95% confidence interval of 0.55 to 1.10. The p-value was 0.158, which was not significant.

Safety and tolerability findings were not reported in the available data. Adverse events, serious adverse events, discontinuations, and general tolerability were not reported. Consequently, specific adverse event rates could not be determined from the input.

A key finding emerged in a subgroup analysis of patients with negative hyperselection, defined as no genomic alteration. In this group, median progression-free survival was 5.35 months with a 95% confidence interval of 4.4 to 5.9 months versus 3.65 months with a 95% confidence interval of 2.8 to 4.8 months. The hazard ratio was 0.62 with a 95% confidence interval of 0.42 to 0.92. The p-value was 0.017, showing a significant improvement. Median overall survival in this subgroup was 15.0 months with a 95% confidence interval of 12.6 to 19.9 months versus 11.1 months with a 95% confidence interval of 8.6 to 15.6 months. The hazard ratio was 0.61 with a 95% confidence interval of 0.39 to 0.97. The p-value was 0.037, indicating a significant improvement.

The study limitations include the observation that the addition of avelumab does not increase efficacy of cetuximab rechallenge in the overall population. This suggests that the combination strategy may not be broadly applicable for all patients in this category. The practice relevance indicates that liquid biopsy CGP identifies patients who benefit from anti-EGFR rechallenge, supporting its implementation in the continuum of care of mCRC. However, the evidence is limited to this specific phase II trial design.

Clinical implications suggest caution when considering the addition of avelumab to cetuximab for rechallenge in metastatic colorectal cancer. The results do not support a broad recommendation for this combination in the general RAS/BRAF wild-type population. Questions remain regarding the specific utility of this combination in the identified subgroup with negative hyperselection and whether larger trials are needed to confirm these findings. The lack of reported safety data limits the ability to assess the risk-benefit profile of the combination therapy.