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SHR Neuro Krebs Kardio Lipid Stoffw Microb
Schumann, K; Klespe, KC; Mauch, C; Loquai, C; Schultheis, U; Börger, S; Thiem, A; Emmert, S; Hoellwerth, M; Koelbinger, P; Nguyen, VA; Wanner, M; Richtig, E; Peitsch, WK; Harth, W; Zenderowski, V; Braun, AD; Mengoni, M; Dummer, R; Mangana, J; Maul, LV; Meis, F; Rappersberger, K; Persa, OD; Biedermann, T; Posch, C.
Switching PD-1 to BRAF + MEK inhibition improves recurrence-free survival in patients receiving a second course of adjuvant melanoma therapy.
J Eur Acad Dermatol Venereol. 2025;
Doi: 10.1111/jdv.20708
Web of Science
PubMed
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- BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.