Dr Truong on Targeted Therapy vs Immunotherapy in BRAF V600–Positive Melanoma

Thach-Giao Truong, MD, medical director, Melanoma Program, Cleveland Clinic, discusses long-term findings from the phase 2 ImmunoCobiVem trial (NCT02902029) investigating early switch from targeted therapy to immunotherapy in patients with advanced BRAF V600–positive melanoma.

ImmunoCobiVem enrolled 185 patients with previously untreated, BRAF V600–mutated unresectable or metastatic melanoma. All patients received the targeted therapy combination vemurafenib (Zelboraf) plus cobimetinib (Cotellic) during a 3-month run-in phase. During the randomization phase, patients were randomly assigned 1:1 to arm A (n = 69), in which they continued to receive vemurafenib plus cobimetinib, or arm B (n = 66), in which they switched to receive the immunotherapy agent atezolizumab (Tecentriq). The primary end point was PFS from the start of the run-in phase until first disease progression (PFS1). The time from first disease progression to second disease progression served as a secondary end point.

Patients in arm A, who switched from the targeted therapy combination to single-agent immunotherapy, had worse PFS1 outcomes vs those in arm B who did not switch therapies and instead continued to receive targeted therapy, Truong begins. This included loss of response after the switch, Truong adds. The median PFS1 was 13.0 months (95% CI, 9.9-15.6) in arm A vs 5.9 months (95% CI, 5.5-8.3) in arm B (HR, 0.61; 95% CI, 0.41-0.91; stratified P = .006). These data indicate that single-agent immunotherapy is not as effective as a targeted therapy combination in the treatment of patients with advanced BRAF V600–positive melanoma, Truong notes.

These findings also further contextualize other datasets in the melanoma field, such as the phase 3 DREAMseq trial (NCT02224781), which investigated dabrafenib (Tafinlar) plus trametinib (Mekinist) followed by nivolumab (Opdivo) plus ipilimumab (Yervoy) vs the reverse sequence in patients with advanced BRAF-mutant melanoma, Truong explains. Other melanoma clinical trials have raised questions about the efficacy of frontline immunotherapy-containing triplet vs doublet regimens, she emphasizes. Overall, research with immunotherapy in melanoma indicates that the efficacy of this treatment class depends on the line of therapy it is administered in, as well as the specific regimen used, Truong concludes.