Hoeijmakers, L. L. and Rozeman, E. A. and Lopez-Yurda, M. and Grijpink-Ongering, L. G. and Heeres, B. C. and van de Wiel, B. A. and Flohil, C. and Sari, A. and Heijmink, S. W. T. P. J. and van den Broek, D. and Broeks, A. and de Groot, J. W. B. and Vollebergh, M. A. and Wilgenhof, S. and van Thienen, J. V. and Haanen, J. B. A. G. and Blank, Christian (2025) 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. EUROPEAN JOURNAL OF CANCER, 222: 115431. ISSN 0959-8049, 1879-0852
Full text not available from this repository. (Request a copy)Abstract
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-na & iuml;ve 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 2x1-week (cohort 2), 2x2-weeks (cohort 3), or 1x6-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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | BRAF; DABRAFENIB; IPILIMUMAB; PEMBROLIZUMAB; INHIBITION; TRAMETINIB; EXPRESSION; OUTCOMES; PLACEBO; Melanoma; Targeted therapy; Checkpoint inhibition; BRAF; Intermittent |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Hals-Nasen-Ohren-Heilkunde Medicine > Lehrstuhl für Innere Medizin III (Hämatologie und Internistische Onkologie) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 02 Jun 2026 11:20 |
| Last Modified: | 02 Jun 2026 11:20 |
| URI: | https://pred.uni-regensburg.de/id/eprint/67407 |
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