Abstract | BACKGROUND: METHODS: Eligible 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. RESULTS: 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. CONCLUSIONS: 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 vemurafenib- cobimetinib. (Funded by the National Cancer Institute and others; ClinicalTrials.gov number, NCT03224767.).
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Authors | 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 Jr, Daniel P Cahill, Helen A Shih, Paul D Brown, Sandro Santagata, Fred G Barker 2nd, Evanthia Galanis |
Journal | The New England journal of medicine
(N Engl J Med)
Vol. 389
Issue 2
Pg. 118-126
(Jul 13 2023)
ISSN: 1533-4406 [Electronic] United States |
PMID | 37437144
(Publication Type: Clinical Trial, Phase II, Journal Article)
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Copyright | Copyright © 2023 Massachusetts Medical Society. |
Chemical References |
- BRAF protein, human
- Mitogen-Activated Protein Kinase Kinases
- Proto-Oncogene Proteins B-raf
- Vemurafenib
- cobimetinib
- Antineoplastic Agents
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Topics |
- Humans
- Craniopharyngioma
(drug therapy, genetics)
- Disease Progression
- Mitogen-Activated Protein Kinase Kinases
(antagonists & inhibitors, genetics)
- Pituitary Neoplasms
(drug therapy, genetics)
- Proto-Oncogene Proteins B-raf
(antagonists & inhibitors, genetics)
- Vemurafenib
(adverse effects, therapeutic use)
- Antineoplastic Agents
(adverse effects, therapeutic use)
- Remission Induction
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