Recently, pembrolizumab received FDA approval for use as a single agent in patients with solid tumors that exhibit the mismatch repair–deficient (MMR-D)/microsatellite instable (MSI-H) phenotype. It was the first regulatory approval based on a molecular feature independent of the tumor entity.
The current study of nivolumab, another PD-1 antibody, in MSI-H colorectal cancer confirms the results achieved with pembrolizumab in this cancer and expands our knowledge on the activity of this class of agents in several ways. This phase II study was designed to evaluate response with nivolumab in patients with MSI-high metastatic CRC. Patients were recruited after intolerance of or progression through at least one prior line of therapy. At a median follow-up of 12 months, investigator-assessed objective response was 31.1%. Disease control lasting at least 12 weeks was achieved in 69% of patients. Median duration of response had not been reached, and all responders were alive at the time of analysis.
The study demonstrates that response rates were very similar in patients with Lynch syndrome and those with sporadic BRAF V600E mutation–positive cancers. The activity was also independent of PD-L1 expression levels. In addition, even in patients in whom the MSI-H status could not be confirmed by central testing (likely due to technical reasons), nivolumab showed activity. These data suggest that nivolumab can provide durable responses and disease control in patients with MSI-high metastatic CRC, and could be a new treatment option for these patients.
http://www.thelancet.com/pdfs/journals/lanonc/PIIS1470-2045(17)30422-9.pdf
