Triple Combination Active Against CNS Metastases of BRAFV600-Mutated Melanoma

Source: Cancer Therapy Advisor, June 2022

The combination of atezolizumab and cobimetinib with vemurafenib has good intracranial activity in patients with BRAFV600 mutation-positive melanoma with central nervous system (CNS) metastases, according to research presented at the 2022 ASCO Annual Meeting.

Investigators reported primary results from cohort 2 of the phase 2 TRICOTEL trial ( Identifier: NCT03625141). This cohort evaluated the 3-drug combination in adult patients with stage IV BRAFV600-mutated melanoma having magnetic resonance imaging-confirmed CNS metastases that measured at least 5 mm in at least 1 dimension, including those receiving corticosteroids and/or having symptoms. To enroll, the patients could not have received any previous systemic treatment for metastatic disease.

The 3-drug strategy combines targeted therapy against BRAF (vemurafenib) and MEK (cobimetinib), and immunotherapy (atezolizumab). The patients received vemurafenib (720 mg twice daily), cobimetinib (60 mg once daily, 21 days on, 7 days off), and atezolizumab (840 mg on days 1 and 15 of each 28-day cycle from cycle 2 onward). The primary outcome was intracranial objective response rate (ORR), confirmed with assessments at least 4 weeks apart, as assessed by an independent review committee (IRC