- Combination therapy with atezolizumab, cobimetinib, and vemurafenib (A+C+V) led to improved investigator-assessed progression-free survival (PFS) and duration of response (DOR) vs placebo (Pbo)+C+V.
- The combination was tolerable and manageable.
- A+C+V represents a viable option for previously untreated patients with BRAFV600 mutation-positive advanced melanoma.
Why this matters
- Objective response rates (ORR) with BRAF and MEK inhibitors (BRAFi, MEKi) are high but often short-lived in advance BRAF-mutated melanoma.
- Immune checkpoint inhibitor therapy (CIT) shows lower response rates, but more durable responses.
- Combining BRAFi, MEKi and CIT may overcome clinical limitations of the individual drugs.
- In this phase 3 trial, 514 treatment-naive patients with unresectable stage IIIc/IV melanoma and BRAFV600 mutations were randomized to A+C+V (n=256) or Pbo+C+V (n=258).
- Primary endpoint: investigator-assessed PFS; among secondary endpoints: ORR, DOR, overall survival (OS).
- Funding: F.Hoffman-La Roche Ltd and Genentech.
- Investigator-assessed PFS was 15.1 and 10.6 months in A+C+V and Pbo+C+V groups, respectively (P=.025).
- ORR was similar in the two groups (66.3% with A+C+V and 65.0% with Pbo+C+V).
- Median DOR improved with A+C+V (21.0 months) vs Pbo+C+V (12.6 months).
- OS data were not mature.
- The safety profile of the A+C+V regimen was consistent with the known risk of each individual drug.
“Combination of immune checkpoint blockade with targeted therapy clearly works in certain contexts, but we do not know why. Single cells technologies (scRNA-seq, spatial transcriptomic) could help answer the question” Charles L. Sawyers. Investigator, Howard Hughes Medical Institute; Chair, Human Oncology and Pathogenesis Program. Memorial Sloan Kettering Cancer Center, New York, NY.