Immunotherapy has been a game-changer for many cancers, but for most people with advanced colon cancer, it hasn't worked. Doctors have been searching for clues to predict who might be an exception. A new, deep-dive analysis of an older trial offers a possible answer, but it comes with important caveats.
The study looked back at patients with metastatic microsatellite-stable colorectal cancer—the common type that usually resists immunotherapy. All patients were part of a trial testing alternating cycles of standard chemotherapy with the immunotherapy drug nivolumab. Researchers then checked patients' tumors for two things: a high number of mutations (called tumor mutational burden or TMB) or a specific BRAF gene mutation. They also checked a simple blood test for inflammation (C-reactive protein or CRP).
They found that in the group receiving the chemo-immunotherapy combo, the 17 patients who had either a high TMB or the BRAF mutation had a median time without their cancer getting worse of 19.8 months. That was longer than patients without these features. Even more striking, the 11 patients in this group who also started immunotherapy with normal, non-inflammatory CRP levels had a median progression-free survival of 35.0 months. However, this is a post-hoc analysis—meaning researchers looked for patterns after the trial was over. The subgroups are very small, and these findings are exploratory associations, not proof. The results need to be tested prospectively in new, dedicated studies.