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BRAF–MEK Inhibition in Newly Diagnosed Papillary Craniopharyngiomas

The BRAF–MEK inhibitor combination vemurafenib–cobimetinib produced a partial response in 15 of 16 patients with papillary craniopharyngiomas, a biomarker-driven study shows. All patients who received at least 1 cycle had durable partial or better responses.

The single-group trial included patients who had papillary craniopharyngiomas that tested positive for BRAF mutations, had not undergone radiation therapy previously, and had measurable disease. Vemurafenib–cobimetinib was administered in 28-day cycles, with these effects on a primary endpoint of objective response at 4 months: “Of the 16 patients in the study, 15 (94%; 95% confidence interval [CI], 70 to 100) had a durable objective partial response or better to therapy. The median reduction in the volume of the tumor was 91% (range, 68 to 99). The median follow-up was 22 months (95% CI, 19 to 30) and the median number of treatment cycles was 8. Progression-free survival was 87% (95% CI, 57 to 98) at 12 months and 58% (95% CI, 10 to 89) at 24 months. Three patients had disease progression during follow-up after therapy had been discontinued; none have died. The sole patient who did not have a response stopped treatment after 8 days owing to toxic effects. Grade 3 adverse events that were at least possibly related to treatment occurred in 12 patients, including rash in 6 patients. In 2 patients, grade 4 adverse events (hyperglycemia in 1 patient and increased creatine kinase levels in 1 patient) were reported; 3 patients discontinued treatment owing to adverse events.”

Editorial: “Because many histologically benign tumors respond poorly to conventional anticancer drugs, it was initially hypothesized that this would also be true for targeted agents,” editorialists write. “The results of this new study in BRAF V600E papillary craniopharyngiomas and other recent studies indicate that this is not the case. Indeed, genetically simple tumors are often dependent on single-driver mutations and are less prone than clonally complex cancers to rapidly develop resistance. Finally, this study elegantly illustrates how repurposing drugs that were initially developed for common cancers benefits persons with rare tumors as a result of shared underlying molecular pathogenesis.”

Source: New England Journal of Medicine