FDA Accelerates Approval of Dostarlimab for Subset of Rectal Cancer
The FDA has granted accelerated approval to dostarlimab for adults with operable stage II/III rectal cancer that is mismatch repair-deficient or microsatellite instability-high. This biomarker-defined group makes up roughly 3% of locally advanced rectal cancers, and patients who have a complete response may be able to skip chemotherapy, radiation, and surgery. The decision was supported by the AZUR-1 trial, in which most treated patients had a complete response and avoided surgery for at least a year.
Dostarlimab is a PD-1 inhibitor already approved for endometrial cancer and certain previously treated dMMR solid tumors. The accelerated approval now covers adults with operable stage II/III rectal cancer that is dMMR/MSI-H. Such tumors make up about 3% of locally advanced rectal cancers.
In AZUR-1, 76% of evaluable participants had no detectable cancer at one year or more. After median follow-up exceeding two years, no relapses were reported. Side effects were mostly grade 1/2; fatigue, rash, diarrhea, and itching were most common. Grade 3 events included single cases of diabetes, lung infection, hypothyroidism, encephalitis, and neutropenia, plus one grade 4 febrile neutropenia.
For the roughly 3% of locally advanced rectal cancer patients with dMMR/MSI-H disease, this approval could offer a path to avoid chemotherapy, radiation, and surgery if they have a complete response. That may reduce treatment-related life changes and burdens for patients and families. Wider impact may depend on routine biomarker testing at diagnosis, access to treatment, and confirmatory evidence on long-term relapse risk. It may not change care for most rectal cancer patients.