An article summary I wrote for the recent manuscript:
Brastianos P, Twohy E, Geyer S, et al. BRAF-MEK inhibition in newly diagnosed papillary craniopharyngiomas. N Engl J Med. 2023;389(2):118-126. https://www.nejm.org/doi/full/10.1056/NEJMoa2213329
Background: Craniopharyngiomas, rare and benign but locally aggressive tumors, contribute to severe health detriments (e.g., memory and vision loss) due to their location near the pituitary gland. The location of these tumors makes surgery and/or radiation insufficient treatments for craniopharyngiomas. BRAF-MEK inhibitors could provide safer and more effective treatments for people with craniopharyngiomas, as 90% of these tumors have BRAF V600E-mutations that contribute to tumor progression. BRAF-MEK inhibitors are effective and safe for reducing tumor volume in metastatic melanoma, but the safety and efficacy of these inhibitors have not been tested in people with newly diagnosed craniopharyngiomas.
Methods: This single arm, phase II investigation tested the efficacy and safety of combined vemurafenib and cobimetinib in reducing tumor volume in patients newly diagnosed with craniopharyngioma. Men and women (>18 years) with BRAF V600E mutation positive papillary craniopharyngioma were eligible. Additional eligibility criteria were no prior therapy other than surgery and an Eastern Cooperative Oncology Group (ECOG) score of <2.
Results: 15/16 (94%, 95% CI [70-100]) of patients (mean age, 51 years, 56% female, 69% White) responded to orally administered vemurafenib (960 mg/2x day) and cobmetinib (60 mg/day). After 4 cycles there was a 91% (95% CI [68-99]) volumetric reduction in tumors from baseline. Progression-free survival was 87% (95% CI [57-98]) at 12 months and 58% (95% CI [10-89]) at 22 months. The most common adverse event (AE) possibly related to treatment at grade 3 was maculopapular rash (35%). The most common AEs at grade 4 were increased creatinine kinase level (6%) and hyperglycemia (6%).
Conclusions: Combined vemurabfenib and cobmetinib substantially reduce craniopharyngioma volume after 4 treatment cycles in patients newly diagnosed with papillary craniopharyngiomas. The benefit-risk profile for combined vemurabfenib and cobmetinib in reducing craniopharyngiomas in newly diagnosed patients is favorable.
Short Description: The location of craniopharyngiomas, rare and benign but locally aggressive tumors, near the pituitary gland makes surgery and/or radiation insufficient treatments for these tumors. This phase II trial explored the efficacy and safety of BRAF-MEK inhibitors, vemurabfenib and cobmetinib, in reducing craniopharyngiomas in newly diagnosed patients. Combined vemurabfenib and cobmetinib provides a favorable benefit-risk profile for substantially reducing craniopharyngiomas in this population, with promising progression-free survival for up to 22 months.