• Priscilla K Brastianos, Erin Twohy, Susan Geyer, Elizabeth R Gerstner, Timothy J Kaufmann, Shervin Tabrizi, Brian Kabat, Julia Thierauf, Michael W Ruff, Daniela A Bota, David A Reardon, Adam L Cohen, Macarena I De La Fuente, Glenn J Lesser, Jian Campian, Pankaj K Agarwalla, Priya Kumthekar, Bhupinder Mann, Shivangi Vora, Michael Knopp, A John Iafrate, William T Curry, Daniel P Cahill, Helen A Shih, Paul D Brown, Sandro Santagata, Fred G Barker, and Evanthia Galanis.
• From Massachusetts General Hospital Cancer Center, Harvard Medical School (P.K.B., E.R.G., S.T., J.T., A.J.I., W.T.C., D.P.C., H.A.S., F.G.B.), Dana-Farber Cancer Institute (D.A.R.), and Brigham and Women's Hospital, Harvard Program in Therapeutic Science, Dana-Farber Partners CancerCare (S.S.) - all in Boston; Alliance Statistics and Data Management Center (E.T., S.G., B.K.), Mayo Clinic (T.J.K., M.W.R., P.D.B., E.G.), Rochester, MN; UC Irvine-Chao Family Comprehensive Cancer Center, Orange, CA (D.A.B.); Huntsman Cancer Institute, University of Utah, Salt Lake City (A.L.C.); Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami (M.I.D.L.F.); Wake Forest University School of Medicine, Winston-Salem, NC (G.J.L.); Washington University School of Medicine, St. Louis (J.C.); Rutgers Cancer Institute, New Brunswick, NJ (P.K.A.); Northwestern University, Chicago (P.K.); the Cancer Therapy Evaluation Program, National Cancer Institute, Bethesda, MD (B.M.); and Ohio State University Comprehensive Cancer Center, Columbus (S.V., M.K.).
• N. Engl. J. Med. 2023 Jul 13; 389 (2): 118126118-126.

BackgroundCraniopharyngiomas, primary brain tumors of the pituitary-hypothalamic axis, can cause clinically significant sequelae. Treatment with the use of surgery, radiation, or both is often associated with substantial morbidity related to vision loss, neuroendocrine dysfunction, and memory loss. Genotyping has shown that more than 90% of papillary craniopharyngiomas carry BRAF V600E mutations, but data are lacking with regard to the safety and efficacy of BRAF-MEK inhibition in patients with papillary craniopharyngiomas who have not undergone previous radiation therapy.MethodsEligible patients who had papillary craniopharyngiomas that tested positive for BRAF mutations, had not undergone radiation therapy previously, and had measurable disease received the BRAF-MEK inhibitor combination vemurafenib-cobimetinib in 28-day cycles. The primary end point of this single-group, phase 2 study was objective response at 4 months as determined with the use of centrally determined volumetric data.ResultsOf 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.ConclusionsIn this small, single-group study involving patients with papillary craniopharyngiomas, 15 of 16 patients had a partial response or better to the BRAF-MEK inhibitor combination vemurafenib-cobimetinib. (Funded by the National Cancer Institute and others; ClinicalTrials.gov number, NCT03224767.).Copyright © 2023 Massachusetts Medical Society.

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