Background: The addition of targeted therapy (TT) to immune checkpoint inhibitors has been shown to transiently increase immune infiltration in melanoma. This formed the rationale for the IMPemBra trial, which showed a numerical increase in progression-free survival (PFS) in patients treated with short-term/intermittent TT and anti-PD1 compared to anti-PD1 alone. In this report, the final toxicity-analysis, 5-year PFS and exploratory analysis of overall survival (OS) will be reported, together with an analysis of subsequent therapies.
Patients and methods: 32 treatment-naïve patients with a BRAFV600E/K-mutated advanced melanoma were treated with 2 cycles of pembrolizumab 200 mg every 3 weeks, followed by randomization to continue pembrolizumab monotherapy for six weeks in cohort-1 versus pembrolizumab plus intermittent dabrafenib 150 mg BID + trametinib 2 mg QD 2×1-week (cohort 2), 2×2-weeks (cohort 3), or 1×6-weeks (cohort 4). After week 12, all patients continued pembrolizumab monotherapy for a maximum of 2 years.
Results: With a median follow-up of 73 months, final grade 3-4 immune-related adverse events are 12 % (cohort 1), 12 % (cohort 2), 38 % (cohort 3) and 63 % (cohort 4). Estimated 5-year PFS and OS rates were 25 % and 50 % for pembrolizumab monotherapy (cohort-1) and 46 % and 71 % for pembrolizumab + intermittent TT (cohorts 2-4). Estimated 5-year PFS and OS were 63 % and 63 % (cohort 2), 38 % and 75 % (cohort 3), and 38 % and 75 % (cohort 4), respectively. The subsequent therapies were balanced between cohorts. Patients treated with short-term/intermittent schemes achieved durable responses upon subsequent TT again.
Conclusion: This survival update from the IMPemBra trial demonstrates that combination of short-term TT and checkpoint inhibition can induce long-lasting responses, warranting further analyses in larger cohorts, and in a randomized design.
Keywords: BRAF; Checkpoint inhibition; Intermittent; Melanoma; Targeted therapy.
Copyright © 2025. Published by Elsevier Ltd.