- Email: [email protected]
Phase 3, Double-Blind, Placebo-Controlled Study of Vemurafenib Versus Vemurafenib + Cobimetinib in Previously Untreated Brafv600 Mutation–Positive Patients with Unresectable Locally Advanced or Metastatic Melanoma (Nct01689519)
Annals of Oncology 25 (Supplement 5): v1–v41, 2014 doi:10.1093/annonc/mdu438.40
LBA5 PR
abstracts
G.A. McArthur1, P.A. Ascierto2, J. Larkin3, A. Ribas4, G. Liszkay5, M. Maio6, M. Mandalà7, L.V. Demidov8, D. Stroyakovsky9, L. Thomas10, L. De La Cruz Merino11, V. Atkinson12, C. Dutriaux13, C. Garbe14, I. Chang15, S.P. Hack16, B. Dréno17 1 Cancer Therapeutics, Peter MacCallum Cancer Centre, East Melbourne, VIC, Australia 2 Melanoma, Cancer Immunotherapy and Innovative Therapies, Istituto Nazionale Tumori Fondazione “G. Pascale”, Napoli, ITALY 3 Department of Medicine, Royal Marsden Hospital, London, UK 4 Department of Medicine, UCLA, Los Angeles, CA, USA 5 Oncodermatology, National Institute of Oncology, Budapest, HUNGARY 6 Oncology, University Hospital of Siena, Siena, ITALY 7 Oncology and Hematology, Papa Giovanni XXIII Hospital, Bergamo, ITALY 8 Tumor Biotherapy, NN Blokhin Russian Cancer Research Center, Moscow, RUSSIAN FEDERATION 9 Chemotherapy, Moscow City Oncology Hospital # 62, Istra, RUSSIAN FEDERATION 10 Dermato-oncology, Centre Hospitalier Lyon Sud, Rhone, FRANCE 11 Clinical Oncology, Hospital Universitario Virgen Macarena, Sevilla, SPAIN 12 Division of Cancer Services, Princess Alexandra Hospital, Woolloongabba, AUSTRALIA 13 Dermato-oncology, Hôpital Saint André, Bordeaux, FRANCE 14 Dermatology, University of Tubingen, Tubingen, GERMANY 15 Product Development, Roche, South San Francisco, CA, USA
Background: Combined inhibition of BRAF and MEK is hypothesized to improve clinical outcomes by preventing or delaying the onset of resistance observed with BRAF inhibitors alone. This randomized phase 3 study evaluated the combination of the BRAF inhibitor vemurafenib and the MEK inhibitor cobimetinib. Methods: Between January 2013 and January 2014, 495 patients ( pts) were randomly assigned to receive vemurafenib + cobimetinib or vemurafenib + placebo. In a 28–day treatment cycle, vemurafenib was administered at 960 mg twice daily from Days 1-28 and cobimetinib or placebo was administered at 60 mg daily from Days 1–21. Eligibility included treatment-naive BRAFV600 mutation–positive pts with unresectable locally advanced or metastatic melanoma and adequate performance status and organ function. Primary end point was investigator-assessed progression-free survival (PFS). Results: Median PFS was 9.9 months with the combination compared with 6.2 months in the control arm (hazard ratio [HR] = 0.51; 95% confidence interval [CI], 0.39–0.68; P <0.0001). The rate of complete and partial response was 68% in the combination arm and 45% in the control arm (P <0.0001), including complete response in 10% of pts treated with the combination and 4% of pts in the control group. Subgroup analyses of PFS based on key demographic and tumor characteristics were consistent with PFS in the intent-to-treat population. PFS assessed by independent review was comparable with investigator-assessed PFS. Interim overall survival (OS) data showed an HR of 0.65 (95% CI, 0.42–1.00) but did not cross the prespecified stopping boundary. Vemurafenib + cobimetinib combination, compared with vemurafenib alone, was associated with a higher incidence of grade ≥ 3 adverse events ([AEs] 65% vs 59%); however, there was no difference in the rate of AEs leading to study drug discontinuation and there was a decrease in the occurrence of secondary cutaneous neoplasms with the combination.
Downloaded from https://academic.oup.com/annonc/article-abstract/25/suppl_4/mdu438.40/1746503 by guest on 24 October 2019
PHASE 3, DOUBLE-BLIND, PLACEBO-CONTROLLED STUDY OF VEMURAFENIB VERSUS VEMURAFENIB + COBIMETINIB IN PREVIOUSLY UNTREATED BRAFV600 MUTATION–POSITIVE PATIENTS WITH UNRESECTABLE LOCALLY ADVANCED OR METASTATIC MELANOMA (NCT01689519)
16 Product Development (oncology), Roche/Genentech, South San Francisco, CA, USA 17 Department of Dermato Cancerology, CHU Nantes - Nantes Hospital University, Nantes, FRANCE
© The Author 2014. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: [email protected].
LBA5 PR
abstracts
G.A. McArthur1, P.A. Ascierto2, J. Larkin3, A. Ribas4, G. Liszkay5, M. Maio6, M. Mandalà7, L.V. Demidov8, D. Stroyakovsky9, L. Thomas10, L. De La Cruz Merino11, V. Atkinson12, C. Dutriaux13, C. Garbe14, I. Chang15, S.P. Hack16, B. Dréno17 1 Cancer Therapeutics, Peter MacCallum Cancer Centre, East Melbourne, VIC, Australia 2 Melanoma, Cancer Immunotherapy and Innovative Therapies, Istituto Nazionale Tumori Fondazione “G. Pascale”, Napoli, ITALY 3 Department of Medicine, Royal Marsden Hospital, London, UK 4 Department of Medicine, UCLA, Los Angeles, CA, USA 5 Oncodermatology, National Institute of Oncology, Budapest, HUNGARY 6 Oncology, University Hospital of Siena, Siena, ITALY 7 Oncology and Hematology, Papa Giovanni XXIII Hospital, Bergamo, ITALY 8 Tumor Biotherapy, NN Blokhin Russian Cancer Research Center, Moscow, RUSSIAN FEDERATION 9 Chemotherapy, Moscow City Oncology Hospital # 62, Istra, RUSSIAN FEDERATION 10 Dermato-oncology, Centre Hospitalier Lyon Sud, Rhone, FRANCE 11 Clinical Oncology, Hospital Universitario Virgen Macarena, Sevilla, SPAIN 12 Division of Cancer Services, Princess Alexandra Hospital, Woolloongabba, AUSTRALIA 13 Dermato-oncology, Hôpital Saint André, Bordeaux, FRANCE 14 Dermatology, University of Tubingen, Tubingen, GERMANY 15 Product Development, Roche, South San Francisco, CA, USA
Background: Combined inhibition of BRAF and MEK is hypothesized to improve clinical outcomes by preventing or delaying the onset of resistance observed with BRAF inhibitors alone. This randomized phase 3 study evaluated the combination of the BRAF inhibitor vemurafenib and the MEK inhibitor cobimetinib. Methods: Between January 2013 and January 2014, 495 patients ( pts) were randomly assigned to receive vemurafenib + cobimetinib or vemurafenib + placebo. In a 28–day treatment cycle, vemurafenib was administered at 960 mg twice daily from Days 1-28 and cobimetinib or placebo was administered at 60 mg daily from Days 1–21. Eligibility included treatment-naive BRAFV600 mutation–positive pts with unresectable locally advanced or metastatic melanoma and adequate performance status and organ function. Primary end point was investigator-assessed progression-free survival (PFS). Results: Median PFS was 9.9 months with the combination compared with 6.2 months in the control arm (hazard ratio [HR] = 0.51; 95% confidence interval [CI], 0.39–0.68; P <0.0001). The rate of complete and partial response was 68% in the combination arm and 45% in the control arm (P <0.0001), including complete response in 10% of pts treated with the combination and 4% of pts in the control group. Subgroup analyses of PFS based on key demographic and tumor characteristics were consistent with PFS in the intent-to-treat population. PFS assessed by independent review was comparable with investigator-assessed PFS. Interim overall survival (OS) data showed an HR of 0.65 (95% CI, 0.42–1.00) but did not cross the prespecified stopping boundary. Vemurafenib + cobimetinib combination, compared with vemurafenib alone, was associated with a higher incidence of grade ≥ 3 adverse events ([AEs] 65% vs 59%); however, there was no difference in the rate of AEs leading to study drug discontinuation and there was a decrease in the occurrence of secondary cutaneous neoplasms with the combination.
Downloaded from https://academic.oup.com/annonc/article-abstract/25/suppl_4/mdu438.40/1746503 by guest on 24 October 2019
PHASE 3, DOUBLE-BLIND, PLACEBO-CONTROLLED STUDY OF VEMURAFENIB VERSUS VEMURAFENIB + COBIMETINIB IN PREVIOUSLY UNTREATED BRAFV600 MUTATION–POSITIVE PATIENTS WITH UNRESECTABLE LOCALLY ADVANCED OR METASTATIC MELANOMA (NCT01689519)
16 Product Development (oncology), Roche/Genentech, South San Francisco, CA, USA 17 Department of Dermato Cancerology, CHU Nantes - Nantes Hospital University, Nantes, FRANCE
© The Author 2014. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: [email protected].