Adjuvantly treated stage III melanoma patients under real-world conditions: treatment and outcome

June 28, 2023

Abstract

Purpose:
Clinical trials demonstrated significantly improved recurrence-free survival (RFS) of melanoma patients receiving adjuvant treatment. As data from controlled trials are based on selected populations, we investigated adjuvantly treated stage III melanoma patients under real-world conditions.

Patients and methods:
In a prior multicenter cohort study, stage III-IV melanoma patients had been analyzed for their choice of adjuvant therapy. In this follow-up study, we examined RFS, overall and melanoma-specific survival (MSS) and response to subsequent treatment of 589 stage III patients (232 BRAF-mutated) receiving adjuvant PD-1 inhibitors (PD1; n=479) or targeted therapy (TT; n=110).

Results:
Median follow-up of the total cohort was 25.7 months. Main reason for premature discontinuation of adjuvant therapy was disease progression in PD1- (28.8%, n=138/479) and adverse events in TT-treated patients (28.2%, n=31/110).
Among BRAF-mutated patients, RFS at 24 months was 49% (95% CI 40.6-59.0%) for PD1- and 67% (95% CI 58-77%) for TT-treated patients. Risk of recurrence was higher for BRAF-mutated PD1 than TT (hazard ratio 1.99; 95% CI 1.34-2.96; hazard ratio adjusted for age, sex and tumor stage, 2.21; 95% CI 1.48-3.30). 24-month MSS were 87% (95% CI 81.0-94.1) for PD1 and 92% (95% CI 86.6-97.0) for TT.
Response to subsequent systemic treatment for unresectable disease was 22% for all PD1- and 16% for TT-treated patients.

Conclusions:
PD1-treated patients had more and earlier recurrences than TT patients. In BRAF-mutated patients adjuvant TT might prevent early recurrences more effectively than PD1 treatment. Management of recurrence despite adjuvant treatment is challenging with low response to current therapeutic options.

Data availability statement:
The datasets generated during and/or analyzed during the current study are available for qualified researchers from the corresponding authors upon request.

Source:

Georg C. Lodde, Jessica Hassel, Lena M. Wulfken, Friedegund Meier, Peter Mohr, Katharina Kähler, Axel Hauschild, Bastian Schilling, Carmen Loquai, Carola Berking, Svea Hüning, Julia Eckardt, Ralf Gutzmer, Lydia Reinhardt, Valerie Glutsch, Ulrike Nikfarjam, Michael Erdmann, Catharina L. Beckmann, Andreas Stang, Bernd Kowall, Wolfgang Galetzka, Alexander Roesch, Selma Ugurel, Lisa Zimmer, Dirk Schadendorf, Andrea Forschner, Elisabeth Livingstone, Adjuvant treatment and outcome of stage III melanoma patients: Results of a multicenter real-world DeCOG study, European Journal of Cancer, 2023, 112957, ISSN 0959-8049, 
https://doi.org/10.1016/j.ejca...

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