Journal Article

DKFZ-2023-01425

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png 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.

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

2023
Elsevier Amsterdam [u.a.]

This record in other databases:  

Please use a persistent id in citations: doi:10.1016/j.ejca.2023.112941

Abstract: 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.In this multicenter phase 2 study, patients received vemurafenib plus cobimetinib. After 3months, 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.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 5.9months; 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.In patients with BRAFV600-mutated advanced melanoma who achieve tumour control with TT, early switch at 3months to atezolizumab led to rapid loss of tumour control but provided a numerical OS benefit at 2years compared with continued TT.

Keyword(s): Checkpoint inhibition ; First-line ; Melanoma ; Run-in ; Sequence ; Targeted therapy

---

Contributing Institute(s):

1. DKTK Koordinierungsstelle Essen/Düsseldorf (ED01)
2. KKE Dermatoonkologie (A370)

Research Program(s):

1. 311 - Zellbiologie und Tumorbiologie (POF4-311) (POF4-311)

Appears in the scientific report 2023

---

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

---