Schumann, Katharina and Klespe, Kai Christian and Mauch, Cornelia and Loquai, Carmen and Schultheis, Ulrike and Boerger, Sevil and Thiem, Alexander and Emmert, Steffen and Hoellwerth, Magdalena and Koelbinger, Peter and Nguyen, Van Anh and Wanner, Marina and Richtig, Erika and Peitsch, Wiebke K. and Harth, Wolfgang and Zenderowski, Veronika and Braun, Andreas Dominik and Mengoni, Miriam and Dummer, Reinhard and Mangana, Johanna and Maul, Lara Valeska and Meis, Frank and Rappersberger, Klemens and Persa, Oana Diana and Biedermann, Tilo and Posch, Christian (2025) Switching PD-1 to BRAF + MEK inhibition improves recurrence-free survival in patients receiving a second course of adjuvant melanoma therapy. JOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY AND VENEREOLOGY, 39 (11). pp. 1987-1996. ISSN 0926-9959, 1468-3083
Full text not available from this repository. (Request a copy)Abstract
BackgroundPD-1 or BRAF + MEK inhibition is considered the current gold standard in adjuvant melanoma therapy. Little is known if, after the recurrence of the disease and surgery, a second course of adjuvant therapy might be beneficial.MethodsA multicenter, retrospective study investigating a second course of adjuvant therapy after recurrence and surgery in stage III-IV melanoma patients. Patients received nivolumab (NIV), pembrolizumab (PEM) or dabrafenib plus trametinib (D + T) between 01/2017 and 10/2021. The primary endpoint was 12-month recurrence-free survival (RFS2). Further analyses included descriptive and correlative statistics.ResultsSixty-six patients from 22 centers in Germany, Austria and Switzerland were included. Thirty-two patients received D + T as second-course adjuvant therapy, 9 patients received PEM and 25 patients received NIV. Recurrence-free survival for the second-course adjuvant treatment (RFS2) was assessed after 12 and 24 months and showed a superiority of adjuvant BRAF + MEK over PD-1 therapy (12-months RFS2: 90.6% vs. 70.6%, HR 4.226 [95% CI 1.154-15.48]; p = 0.030; 24-months RFS2 71.9% vs. 52.9%, HR 3.154 [95% CI 1.374-7.242]; p = 0.007). There was no significant decrease in OS with either BRAF + MEK or PD-1 treatment (12-months OS: 100% both, 24-months OS: 100% vs. 93.8%). Furthermore, therapy sequences were investigated. For better comparability, only BRAF V600 mutated patients were assessed: RFS2 was significantly better for patients with a class switch from PD-1 to BRAF + MEK compared to BRAF + MEK to PD-1 (HR 4.401 (1.04-18.63), p = 0.044). No new safety signals were detected.ResultsSixty-six patients from 22 centers in Germany, Austria and Switzerland were included. Thirty-two patients received D + T as second-course adjuvant therapy, 9 patients received PEM and 25 patients received NIV. Recurrence-free survival for the second-course adjuvant treatment (RFS2) was assessed after 12 and 24 months and showed a superiority of adjuvant BRAF + MEK over PD-1 therapy (12-months RFS2: 90.6% vs. 70.6%, HR 4.226 [95% CI 1.154-15.48]; p = 0.030; 24-months RFS2 71.9% vs. 52.9%, HR 3.154 [95% CI 1.374-7.242]; p = 0.007). There was no significant decrease in OS with either BRAF + MEK or PD-1 treatment (12-months OS: 100% both, 24-months OS: 100% vs. 93.8%). Furthermore, therapy sequences were investigated. For better comparability, only BRAF V600 mutated patients were assessed: RFS2 was significantly better for patients with a class switch from PD-1 to BRAF + MEK compared to BRAF + MEK to PD-1 (HR 4.401 (1.04-18.63), p = 0.044). No new safety signals were detected.ConclusionIn the investigated cohort, a second course of adjuvant melanoma treatment is feasible and provides similar RFS compared to an initial course of adjuvant therapy using BRAF + MEK inhibitors; however, RFS2 is reduced for PD-1 antibodies. In addition, both treatments were convincing with a 24-month OS of almost 100%. Switching from adjuvant PD-1 to BRAF + MEK treatment provided better overall RFS compared to switching from adjuvant BRAF + MEK to PD-1 treatment.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | DABRAFENIB PLUS TRAMETINIB; DOUBLE-BLIND; MELANOMA; PHASE-3; SURVIVAL; PEMBROLIZUMAB; MULTICENTER; IPILIMUMAB; PLACEBO; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Dermatologie und Venerologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 01 Apr 2026 08:23 |
| Last Modified: | 01 Apr 2026 08:23 |
| URI: | https://pred.uni-regensburg.de/id/eprint/67780 |
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