Addition of Short-Term Targeted Therapy Provides Long-Term Survival Benefit for Patients With Advanced Melanoma
According to updated survival results from the IMPemBra trial, the addition of short-term targeted therapy to anti-PD1 inhibition demonstrated long-term survival benefit among treatment-naive patients with BRAFV600E/K-mutated advanced melanoma.
In this study, 32 patients received 200 mg of pembrolizumab once every 3 weeks for 2 cycles. Patients were then randomized to continue pembrolizumab monotherapy for 6 weeks (cohort 1) or undergo pembrolizumab plus 150 mg of dabrafenib and 2 mg of trametinib either twice weekly for 1 week (cohort 2), twice weekly for 2 weeks (cohort 3), or once weekly for 6 weeks (cohort 4) for up to 12 weeks. Patients then continued pembrolizumab monotherapy for up to 2 years. The primary end point was safety. Key secondary end points included progression-free survival (PFS) and overall survival (OS).
At a median follow-up of 73 months, immune-related adverse events occurred in 12% of patients in cohorts 1 and 2, 38% of patients in cohort 3, and 63% of patients in cohort 4. In cohort 1, estimated 5-year PFS rate was 25% and estimated 5-year OS rate was 50%. Estimated 5-year PFS and OS rates were 63% and 63% in cohort 2, 38% and 75% in cohort 3, and 38% and 75% in cohort 4.
“This survival update from the IMPemBra trial demonstrates that combination of short-term [targeted therapy] and checkpoint inhibition can induce long-lasting responses, warranting further analyses in larger cohorts, and in a randomized design,” concluded Dr Hoeijmakers et al.
Source:
Hoeijmakers LL, Rozeman EA, Lopez-Yurda M, et al. Durable responses upon short-term addition of targeted therapy to anti-PD1 in advanced melanoma patients: 5-year progression-free and overall survival update of the IMPemBra trial. Eur J Cancer. Published online: April 18, 2025. doi: 10.1016/j.ejca.2025.115431
