Does Immunotherapy Offer Survival Advantage in Resected Cutaneous Melanoma?
Posted: Monday, March 16, 2020
The phase III E1609 trial, published in the Journal of Clinical Oncology, found that patients with resected cutaneous melanoma who were treated with adjuvant ipilimumab at 3 mg/kg seemed to achieve better overall survival outcomes than patients treated with the active control regimen, high-dose interferon alfa-2b. Ahmad A. Tarhini, MD, PhD, of the H. Lee Moffitt Comprehensive Cancer Center, Tampa, Florida, and colleagues also reported that, although ipilimumab at 10 mg/kg is the approved adjuvant therapy dosage, patients experienced greater toxicity and inferior efficacy than high-dose interferon alfa-2b.
The research team randomly assigned 1,670 adults with resected cutaneous melanoma to receive ipilimumab at 3 mg/kg (n = 523), ipilimumab at 10 mg/kg (n = 511), or high-dose interferon alfa-2b (n = 636). Using a two-step hierarchical approach, the researchers first evaluated ipilimumab at 3 mg/kg versus high-dose interferon alfa-2b and then ipilimumab at 10 mg/kg versus high-dose interferon alfa-2b.
Grade 3 or higher treatment-related adverse events were reported in 37% of patients in the low-dose ipilimumab arm, 79% in the interferon arm, and 58% in the high-dose ipilimumab arm. Adverse events led to treatment discontinuation in 35%, 20%, and 54% of patients, respectively. An intent-to-treat analysis of ipilimumab at 3 mg/kg versus interferon significantly favored ipilimumab (P = .044). In cases with disease progression, there were significantly higher rates of salvage ipilimumab use after high-dose interferon alfa-2b than low-dose or high-dose ipilimumab (P < .001). Additionally, there was a substantial amount of treatment crossover from interferon to low-dose ipilimumab, suggesting the team’s results of the benefits of ipilimumab at 3 mg/kg may have been conservative.
In the second step of the analysis, no significant survival trends favored the use of ipilimumab at 10 mg/kg. The researchers speculated that increased toxicities in patients treated with higher-dose ipilimumab may have affected outcomes.
Disclosure: For full disclosures of the study authors, visit ascopubs.org.