Early switch from run-in treatment with vemurafenib plus cobimetinib to atezolizumab after 3 months leads to rapid loss of tumour control in patients with advanced BRAFV600-positive melanoma: The ImmunoCobiVem phase 2 randomised trial

E. Livingstone, H. Gogas, L. Kandolf-Sekulovic, F. Meier, T. K. Eigentler, M. Ziemer, P. A.M. Terheyden, A. H. Gesierich, R. A. Herbst, K. C. Kähler, D. C. Ziogas, Z. Mijuskovic, M. Garzarolli, C. Garbe, A. Roesch, S. Ugurel, R. Gutzmer, J. J. Grob, F. Kiecker, J. UtikalC. Windemuth-Kieselbach, S. Eckhardt, L. Zimmer, D. Schadendorf*

*Corresponding author for this work

Abstract

Aim: ImmunoCobiVem investigated whether a planned switch to atezolizumab after achieving tumour control during run-in with vemurafenib + cobimetinib improves progression-free survival (PFS) and overall survival (OS) compared to continuous targeted therapy (TT) in patients with previously untreated advanced BRAFV600-mutated melanoma. Methods: In this multicenter phase 2 study, patients received vemurafenib plus cobimetinib. After 3 months, patients without progressive disease (PD) were randomly assigned (1:1) to continue vemurafenib + cobimetinib (Arm A) or switch to atezolizumab (Arm B) until first documented PD (PD1). Primary outcome was PFS1 (time from start of run-in until PD1 or death). OS and safety were also assessed. Results: Of 185 patients enroled between November 2016 and December 2019, 135 were randomly assigned after the run-in period (Arm A, n = 69; Arm B, n = 66). Median PFS1 was significantly longer in Arm A versus Arm B (13.9 versus 5.9 months; hazard ratio [HR] 0.55; 95% confidence interval [CI], 0.37–0.84; PStratified = 0.001). Median OS was not reached in either arm (HR 1.22; 95%CI, 0.69–2.16; PStratified = 0.389); 2-year OS was higher in Arm B versus Arm A (67%; 95%CI, 53–78 versus 58%; 95%CI, 45–70). Grade 3/4 AEs occurred in 55% of patients in Arm A and 64% in Arm B; treatment-related AEs led to discontinuation of any drug in 7% and 9% of patients, respectively. Conclusion: In patients with BRAFV600-mutated advanced melanoma who achieve tumour control with TT, early switch at 3 months to atezolizumab led to rapid loss of tumour control but provided a numerical OS benefit at 2 years compared with continued TT.

Original languageEnglish
Article number112941
JournalEuropean Journal of Cancer
Volume190
ISSN0959-8049
DOIs
Publication statusPublished - 09.2023

Research Areas and Centers

  • Research Area: Luebeck Integrated Oncology Network (LION)
  • Centers: University Cancer Center Schleswig-Holstein (UCCSH)

DFG Research Classification Scheme

  • 205-14 Haematology, Oncology
  • 205-19 Dermatology

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