COMBINATION THERAPY FOR MELANOMA TREATMENT

A phase II study has shown that the addition of the oncolytic viral agent talimogene laherparepvec (Imlygic) to ipilimumab (Yervoy) significantly increased the response rate in patients with advanced unresectable melanoma. These findings were reported in the Journal of Clinical Oncology by Chesney et al.

Study Details

In the open-label trial, 198 patients with unresectable stage IIIB to IV melanoma and measurable/injectable disease from 45 sites in the United States, France, and Germany were randomized between August 2013 and February 2016 to receive talimogene laherparepvec plus ipilimumab (n = 98) or ipilimumab alone (n = 100). Patients had to have no more than one prior therapy if they had BRAF wild-type tumors or no more than two prior therapies if they had BRAF-mutant tumors. Talimogene laherparepvec was given at a first intralesional dose of ≤ 4 mL x 106 plaque-forming units/mL in week 1, followed by ≤ 4 mL x 108 plaque-forming units/mL at week 4 and every 2 weeks thereafter. Ipilimumab was given at 3 mg/kg every 3 weeks for up to four doses beginning at week 1 in the ipilimumab-alone group and week 6 in the combination group. The primary endpoint was investigator-assessed objective response rate on immune-related response criteria.

Response Rates

Objective response was observed in 38 patients (39%) in the combination group vs 18 patients (18%) in the ipilimumab group (odds ratio = 2.9, P = .002). Responses were not limited to injected lesions, with reductions in visceral lesions being observed in 52% vs 23% of patients. Response rates were 42% vs 10% among 122 patients with BRAF wild-type disease and 34% vs 32% among 69 patients with BRAF-mutant tumors. The median response duration was not reached in either group.

Adverse Events

Common adverse events of any grade in the combination group included fatigue (59% vs 42%), chills (53% vs 3%), and diarrhea (42% vs 35%). Grade ≥ 3 adverse events occurred in 45% vs 35%. Grade ≥ 3 ipilimumab-related adverse events occurred in 19% vs 18%, with the most common being gastrointestinal disorders including colitis (5% vs 4%), diarrhea (3% vs 3%), and autoimmune colitis (2% vs 3%). Grade ≥ 3 talimogene laherparepvec–related adverse events occurred in 15% of patients, with the most common being influenza-like illness (4%) and lymphopenia (4%). Fatal adverse events occurred in three patients in the combination group, with none considered related to treatment.

The investigators concluded: “The study met its primary end point; the objective response rate was significantly higher with talimogene laherparepvec plus ipilimumab versus ipilimumab alone. These data indicate that the combination has greater antitumor activity without additional safety concerns versus ipilimumab.”