A variety of noncolorectal cancers were identified as having mismatch repair (MMR) deficiency in the NCI-MATCH study,1 and a little more than one-third of these cancers responded to treatment with anti–PD-1 therapy nivolumab.
NCI-MATCH treated patients with relapsed or refractory malignancies and assigned patients to receive a targeted therapy based on tumor molecular alterations. Nivolumab had previously shown activity in MMR-deficient colorectal cancers, so here, researchers tested if the drug would also have activity in MMR-deficient noncolorectal cancers.
The researchers screened 4902 patients and found that 2% were MMR-deficient. Forty-two patients were enrolled and treated with nivolumab 3 mg/kg every 2 weeks and 480 mg every 4 weeks after cycle 4.
The most common malignancies included endometrioid endometrial adenocarcinoma, prostate adenocarcinoma, and uterine carcinosarcoma. The overall response rate was 36%. An additional one-fifth of patients had stable disease. Three patients had a complete response (7%) and 13 patients (29%) had partial responses.
According to the researchers, “the response rate of 36% compares well with the previously reported 31% response rate for nivolumab in MMR-deficient colorectal cancer.”
Thirty-three of the 42 patients discontinued treatment, and 9 continued treatment at the time of the study report. Those patients that continued therapy had the best responses.
The estimated progression-free survival at 6 months was 51.3%. At 12 months, this was 46.2%, and at 18 months, 31.4%. Median overall survival was 17.3 months.
“These data confirm the benefit of the anti–PD-1 inhibitor nivolumab in patients with MMR-deficient, noncolorectal cancer,” the researchers concluded.
Disclosure: Most of the authors listed disclosed financial relationships with the pharmaceutical industry and medical device companies. For a full list of disclosures, please refer to the original study.
Azad NS, Gray RJ, Overman MJ, et al. Nivolumab is effective in mismatch repair-deficient noncolorectal cancers: results from arm Z1D—a subprotocol of the NCI-Match (EAY131) Study [published online November 25, 2019]. J Clin Oncol. doi: 10.1200/JCO.19.00818