12 of 12 Patients With Mismatch Repair-Deficient, Locally Advanced Rectal Cancer Had Complete Response to Dostarlimab Alone
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12 of 12 Patients With Mismatch Repair-Deficient, Locally Advanced Rectal Cancer Had Complete Response to Dostarlimab Alone

Douglas K. Rex, MD, MASGE, reviewing Cercek A, et al. N Engl J Med 2022 Jun 5.

It is well known that mismatch repair-deficient colorectal cancer (CRC), also called microsatellite instability (MSI)-high CRC, fails to respond to traditional fluorouracil-based chemotherapy but has substantial response rates to programmed cell death (PD)-1 blockade, also called immune checkpoint inhibitor therapy.

This study examined the response to a PD-1 blocker in 12 patients with locally advanced rectal cancer and confirmed MSI-high tumors. None of the tumors had BRAF mutations, indicating they did not arise through the serrated pathway, and most had germline mutations in Lynch genes, though none of the patients had a family history of Lynch syndrome. 

All 12 patients had a complete response to dostarlimab after 6 months of therapy, as judged by rectal magnetic resonance imaging, 18F-fluorodeoxyglucose–positron-emission tomography, digital rectal examination, and endoscopic biopsies. Side effects were not severe and consisted of rash, dermatitis, pruritis, fatigue, and nausea.

Douglas K. Rex, MD, FASGE

COMMENT

This report was heavily covered in the news media, though I did not hear reporters explaining that <10% of rectal cancers have MSI and would be eligible for this treatment. The news here is that all 12 patients having a complete response is important because, until now, a complete response by mismatch repair-deficient tumors to immune checkpoint inhibitors had been seen only in individual patients.

Note to readers: At the time we reviewed this paper, its publisher noted that it was not in final form and that subsequent changes might be made.

CITATION(S)

Cercek A, Lumish M, Sinopoli J, et al. PD-1 blockade in mismatch repair-deficient, locally advanced rectal cancer. N Engl J Med 2022 Jun 5. (Epub ahead of print) (https://doi.org/10.1056/nejmoa2201445)

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