Journal Article

DKFZ-2025-00939

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Switching PD-1 to BRAF + MEK inhibition improves recurrence-free survival in patients receiving a second course of adjuvant melanoma therapy.

Schumann, K.DKFZ* ; Klespe, K. C. ; Mauch, C. ; Loquai, C. ; Schultheis, U. ; Börger, S. ; Thiem, A. ; Emmert, S. ; Hoellwerth, M. ; Koelbinger, P. ; Nguyen, V. A. ; Wanner, M. ; Richtig, E. ; Peitsch, W. K. ; Harth, W. ; Zenderowski, V. ; Braun, A. D. ; Mengoni, M. ; Dummer, R. ; Mangana, J. ; Maul, L. V. ; Meis, F. ; Rappersberger, K. ; Persa, O. D.DKFZ* ; Biedermann, T.DKFZ* ; Posch, C.DKFZ*

2025
Wiley-Blackwell Oxford [u.a.]

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Please use a persistent id in citations: doi:10.1111/jdv.20708

Abstract: PD-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.A 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.Sixty-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.In 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.

Note: 2025 Nov;39(11):1987-1996

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Contributing Institute(s):

1. DKTK Koordinierungsstelle München (MU01)

Research Program(s):

1. 899 - ohne Topic (POF4-899) (POF4-899)

Appears in the scientific report 2025

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Database coverage:
; Clarivate Analytics Master Journal List ; Current Contents - Clinical Medicine ; DEAL Wiley ; Ebsco Academic Search ; Essential Science Indicators ; IF >= 5 ; JCR ; Nationallizenz ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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