Vemurafenib Plus Cobimetinib in Newly Diagnosed Patients With Papillary Craniopharyngiomas

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In a small phase II trial reported in The New England Journal of Medicine, Priscilla K. Brastianos, MD, and colleagues found that the BRAF-MEK inhibitor combination of vemurafenib and cobimetinib produced an objective response in almost all patients with newly diagnosed papillary craniopharyngiomas who had not received prior radiotherapy.

As stated by the investigators, “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.”

Priscilla K. Brastianos, MD

Priscilla K. Brastianos, MD

Study Details

In the Alliance multicenter trial, 16 patients enrolled between February 2018 and March 2020 were treated with vemurafenib at 960 mg twice daily for 28 days and cobimetinib at 60 mg once daily for 21 days in 28-day cycles. The primary endpoint was objective response at 4 months as determined by centrally determined volumetric data.


Volumetric partial response or better was observed in 15 (94%, 95% confidence interval [CI] = 70%–100%) of 16 patients; the sole patient without a response discontinued treatment after 8 days due to toxicity. Median reduction of tumor volume was 91% (range = 68%–99%). 

Median follow-up was 22 months (95% CI = 19–30 months). The estimated percentage of patients who continued to have volumetric response at 12 months was 93% (95% CI = 80%–100%). Estimated progression-free survival on volumetric measurement criteria was 87% (95% CI = 57%–98%) at 12 months and 58% (95% CI = 10%–89%) at 24 months. Overall survival was 100% (95% CI = 69%–100%) at 12 months and 100% (95% CI =16%–100%) at 24 months.


  • Vemurafenib/cobimetinib produced an objective response in 15 of 16 patients.
  • Responses were ongoing at 12 months in 93% of responders.

Adverse Events

Grade 3 adverse events considered related to treatment occurred in 12 patients, most commonly rash (n = 6) and prolonged QT interval, dehydration, and increased alkaline phosphatase level (n = 2 each). Treatment-related adverse events led to discontinuation of treatment in three patients. 

The investigators concluded, “In 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 [of] vemurafenib [and] cobimetinib.”

Dr. Brastianos, of Massachusetts General Hospital Cancer Center, and Evanthia Galanis, MD, of Mayo Clinic, Rochester, are the corresponding authors for The New England Journal of Medicine article.   

Disclosure: The study was funded by the National Cancer Institute and others. For full disclosures of the study authors, visit

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