학술논문
Treatment management for BRAF-mutant melanoma patients with tumor recurrence on adjuvant therapy: a multicenter study from the prospective skin cancer registry ADOREG
Document Type
article
Author
Dirk Schadendorf; Carola Berking; Jessica C Hassel; Lisa Zimmer; Ralf Gutzmer; Alexander Kreuter; Andrea Forschner; Bastian Schilling; Selma Ugurel; Katharina C Kähler; Peter Mohr; Patrick Terheyden; Felix Kiecker; Henner Stege; Sebastian Haferkamp; Friedegund Meier; Claudia Pfoehler; Dirk Debus; Rudolf Herbst; Carmen Loquai; Frank Meiss; Martin Kaatz; Jens Ulrich; Edgar Dippel; Michael Weichenthal; Axel Hauschild; Ulrike Leiter; Markus V Heppt; Christoffer Gebhardt; Michael Sachse; Fabian Ziller; Stephan Grabbe; Georg Lodde; Maximilian Haist; Friederike Rogall; Yuqi Tan; Imke von Wasielewski; Kai Christian Klespe; Michael Tronnier; Jan Christoph Simon
Source
Journal for ImmunoTherapy of Cancer, Vol 11, Iss 9 (2023)
Subject
Language
English
ISSN
2051-1426
Abstract
Background Adjuvant therapy with immune-checkpoint inhibitors (CPI) or BRAF/MEK-directed targeted therapy (TT) improves recurrence-free survival (RFS) for patients with advanced, BRAFV600-mutant (BRAFmut) resected melanoma. However, 40% of these patients will develop distant metastases (DM) within 5 years, which require systemic therapy. Little data exist to guide the choice of upfront adjuvant therapy or treatment management upon DM. This study evaluated the efficacy of subsequent treatments following tumor recurrence upon upfront adjuvant therapy.Methods For this multicenter cohort study, we identified 515 BRAFmut patients with resected stage III melanoma who were treated with PD-1 inhibitors (anti-PD1) or TT in the adjuvant setting. Disease characteristics, treatment regimens, details on tumor recurrence, subsequent treatment management, and survival outcomes were collected within the prospective, real-world skin cancer registry ADOReg. Primary endpoints included progression-free survival (PFS) following DM and best tumor response to first-line (1L) treatments.Results Among 515 eligible patients, 273 patients received adjuvant anti-PD1 and 242 adjuvant TT. At a median follow-up of 21 months, 54.6% of anti-PD1 patients and 36.4% of TT patients recurred, while 39.6% (anti-PD1) and 29.3% (TT) developed DM. Risk of recurrence was significantly reduced in patients treated with TT compared with anti-PD1 (adjusted HR 0.52; 95% CI 0.40 to 0.68, p