Complete response of metastatic microsatellite-stable BRAF V600E colorectal cancer to first-line oxaliplatin-based chemotherapy and immune checkpoint blockade.

The randomized METIMMOX trial (NCT03388190) examined if patients with previously untreated, unresectable abdominal metastases from microsatellite-stable (MSS) colorectal cancer (CRC) might benefit from potentially immunogenic, short-course oxaliplatin-based chemotherapy alternating with immune checkpoint blockade (ICB). Three of 38 patients assigned to this experimental treatment had metastases from BRAF-mutant MSS-CRC, in general a poor-prognostic subgroup explored here. The ≥70-year-old females presented with ascending colon adenocarcinomas with intermediate tumor mutational burden (6.2-11.8 mutations per megabase). All experienced early disappearance of the primary tumor followed by complete response of all overt metastatic disease, resulting in progression-free survival as long as 20-35 months. However, they encountered recurrence at previously unaffected sites and ultimately sanctuary organs, or as intrahepatic tumor evolution reflected in the terminal loss of initially induced T-cell clonality in liver metastases. Yet, the remarkable first-line responses to short-course oxaliplatin-based chemotherapy alternating with ICB may offer a novel therapeutic option to a particularly hard-to-treat MSS-CRC subgroup.