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. Utikal; C. Windemuth-Kieselbach; S. Eckhardt; L. Zimmer; D. Schadendorf

doi:10.1016/j.ejca.2023.112941

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 BRAF^V600-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; P_Stratified = 0.001). Median OS was not reached in either arm (HR 1.22; 95%CI, 0.69–2.16; P_Stratified = 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 BRAF^V600-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 language	English
Article number	112941
Journal	European Journal of Cancer
Volume	190
ISSN	0959-8049
DOIs	https://doi.org/10.1016/j.ejca.2023.112941
Publication status	Published - 09.2023

Funding

This study was funded by F. Hoffmann-La Roche Ltd. Third party funds were provided by F. Hoffmann-La Roche for study co-ordination, documentation, monitoring and analysis. Vemurafenib, cobimetinib and atezolizumab were provided at no cost.

Research Areas and Centers

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

DFG Research Classification Scheme

2.22-14 Hematology, Oncology
2.22-19 Dermatology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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Livingstone, E., 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., Ugurel, S., Gutzmer, R., Grob, J. J., Kiecker, F., ... Schadendorf, D. (2023). 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. European Journal of Cancer, 190, Article 112941. https://doi.org/10.1016/j.ejca.2023.112941

@article{61bf912e57554d61b8c4cd47ba008921,

title = "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",

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.",

author = "E. Livingstone and H. Gogas and L. Kandolf-Sekulovic and F. Meier and Eigentler, \{T. K.\} and M. Ziemer and Terheyden, \{P. A.M.\} and Gesierich, \{A. H.\} and Herbst, \{R. A.\} and K{\"a}hler, \{K. C.\} and Ziogas, \{D. C.\} and Z. Mijuskovic and M. Garzarolli and C. Garbe and A. Roesch and S. Ugurel and R. Gutzmer and Grob, \{J. J.\} and F. Kiecker and J. Utikal and C. Windemuth-Kieselbach and S. Eckhardt and L. Zimmer and D. Schadendorf",

note = "Publisher Copyright: {\textcopyright} 2023 Elsevier Ltd",

year = "2023",

month = sep,

doi = "10.1016/j.ejca.2023.112941",

language = "English",

volume = "190",

journal = "European Journal of Cancer",

issn = "0959-8049",

publisher = "Elsevier Ltd",

}

Livingstone, E, Gogas, H, Kandolf-Sekulovic, L, Meier, F, Eigentler, TK, Ziemer, M, Terheyden, PAM, Gesierich, AH, Herbst, RA, Kähler, KC, Ziogas, DC, Mijuskovic, Z, Garzarolli, M, Garbe, C, Roesch, A, Ugurel, S, Gutzmer, R, Grob, JJ, Kiecker, F, Utikal, J, Windemuth-Kieselbach, C, Eckhardt, S, Zimmer, L & Schadendorf, D 2023, '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', European Journal of Cancer, vol. 190, 112941. https://doi.org/10.1016/j.ejca.2023.112941

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.; Gogas, H.; Kandolf-Sekulovic, L. et al.
In: European Journal of Cancer, Vol. 190, 112941, 09.2023.

Research output: Journal Articles › Journal articles › Research › peer-review

TY - JOUR

T1 - 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

T2 - The ImmunoCobiVem phase 2 randomised trial

AU - Livingstone, E.

AU - Gogas, H.

AU - Kandolf-Sekulovic, L.

AU - Meier, F.

AU - Eigentler, T. K.

AU - Ziemer, M.

AU - Terheyden, P. A.M.

AU - Gesierich, A. H.

AU - Herbst, R. A.

AU - Kähler, K. C.

AU - Ziogas, D. C.

AU - Mijuskovic, Z.

AU - Garzarolli, M.

AU - Garbe, C.

AU - Roesch, A.

AU - Ugurel, S.

AU - Gutzmer, R.

AU - Grob, J. J.

AU - Kiecker, F.

AU - Utikal, J.

AU - Windemuth-Kieselbach, C.

AU - Eckhardt, S.

AU - Zimmer, L.

AU - Schadendorf, D.

PY - 2023/9

Y1 - 2023/9

N2 - 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.

AB - 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.

UR - https://www.scopus.com/pages/publications/85165712411

U2 - 10.1016/j.ejca.2023.112941

DO - 10.1016/j.ejca.2023.112941

M3 - Journal articles

C2 - 37482012

AN - SCOPUS:85165712411

SN - 0959-8049

VL - 190

JO - European Journal of Cancer

JF - European Journal of Cancer

M1 - 112941

ER -

Livingstone E, Gogas H, Kandolf-Sekulovic L, Meier F, Eigentler TK, Ziemer M et al. 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. European Journal of Cancer. 2023 Sept;190:112941. doi: 10.1016/j.ejca.2023.112941

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

Abstract

Funding

Research Areas and Centers

DFG Research Classification Scheme

UN SDGs

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