medwireNews: Nivolumab elicits promising response rates in noncolorectal treatment-refractory cancers with mismatch repair (MMR) deficiency, suggest phase 2 study results.
The PD-1 inhibitor nivolumab has previously shown clinical activity against MMR-deficient colorectal cancers. And the current NCI-MATCH findings now show that nivolumab also has “promising activity in MMR-deﬁcient noncolorectal cancers of a wide variety of histopathologic types,” write Nilofer Azad (Sidney Kimmel Comprehensive Cancer Center, Baltimore, Maryland, USA) and colleagues in the Journal of Clinical Oncology.
The researchers obtained tumor samples, across 19 difference types, from 4902 patients with relapsed or refractory cancer, excluding colorectal cancer, and screened the samples for MMR deficiency, defined as complete loss of MLH1 or MSH2 expression on immunohistochemistry. Of these patients, 99 (2.0%) were found to have an MMR-deficient cancer and 42 patients were enrolled in the study.
Study participants were treated with intravenous nivolumab 3 mg/kg every 2 weeks in 28-day cycles, with the option of switching to nivolumab 480 mg once per cycle after four cycles. The most common tumors were endometrial and prostate adenocarcinoma, seen in 13 and five patients, respectively. All of those with prostate adenocarcinoma had undergone prior therapy with hormonal agents.
Over a median follow-up of 17.3 months, 15 of the participants experienced an objective response, at a rate of 36%, which, the researchers say, “compares well with the previously reported 31% response rate for nivolumab in MMR-deﬁcient colorectal cancer.”
The estimated 6-month progression-free survival rate was 51.3%, declining to 46.2% at 12 months, and 31.4% at 18 months, and the median overall survival was 17.3 months.
Treatment-related adverse events were generally mild and expected. The most common grade 1–3 adverse events were fatigue (40%), anemia (33%), rash (17%), and hypoalbuminemia (17%); there were two grade 4 events (sepsis) and none at grade 5.
Azad and colleagues note that their initial report of this trial with a shorter follow-up showed a lower response rate for nivolumab of 24%.
“These data support the premise that responses to immune therapy continue to occur over time, and patients with stable disease may eventually achieve a clinical [partial response] or [complete response] with continued therapy,” they say.
The researchers conclude: “This study conﬁrms that MMR deﬁciency identiﬁes a group of tumors across a range of anatomic and histopathologic types with a substantial response rate when treated with nivolumab anti–PD-1 therapy.”
By Catherine Booth
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