Abstract 813P
Background
Primary analysis of the phase 3 IMspire150 study (NCT02908672) demonstrated improved progression-free survival with first-line combination treatment with A+V+C vs P+V+C in patients (pts) with previously untreated BRAF V600 mutation–positive advanced melanoma. At the time of primary analysis (median follow-up 18.9 months), numerically lower rates of interval development of CNS mets were also seen with A+V+C vs P+V+C. Here we report updated exploratory analyses of incidence and time to development of CNS mets with A+V+C vs P+V+C with longer follow-up in the IMspire150 study.
Methods
Eligible pts were randomized 1:1 to receive A+V+C or P+V+C. Pts received V+C in cycle 1; A or P were given on day 1 and 15 of each 28-day cycle starting from cycle 2 onwards. Incidence and time to development of CNS mets were evaluated in pts with no history of CNS mets at baseline confirmed by magnetic resonance imaging/computed tomography (MRI/CT). Follow-up MRI/CT assessments were performed during the study as clinically indicated. Time-to-event outcomes were estimated using the Kaplan-Meier method and competing risks analysis.
Results
514 pts were randomly assigned to A+V+C (n=256) or P+V+C (n=258); 244 and 247 pts, respectively, had no history of CNS mets at baseline. With median follow-up of 29.8 months in the A+V+C arm and 22.8 months in the P+V+C arm, CNS mets had developed in 61/244 pts (25%) in the A+V+C arm and 70/247 pts (28%) in the P+V+C arm. Cumulative incidence of CNS mets as site of first progressive disease with A+V+C vs P+V+C was 16% vs 19%, 24% vs 26%, 25% vs 28%, and 28% vs 29% at 12, 24, 36, and 48 months, respectively (stratified hazard ratio [HR] 0.91; 95% CI, 0.64-1.29). Time to first CNS mets was delayed with A+V+C vs P+V+C (HR 0.80; 95% CI, 0.57-1.13). Median time from first detection of CNS mets until death was similar between A+V+C and P+V+C (median 5.3 vs 5.2 months; HR 0.96; 95% CI, 0.65-1.41).
Conclusions
Addition of A to V+C is associated with numerically lower rates for development of CNS mets. The observed risk reduction for CNS mets is consistent with the overall benefit observed for A+V+C in the IMspire150 study.
Clinical trial identification
NCT02908672.
Editorial acknowledgement
Editorial assistance was provided by Melanie Sweetlove, MSc (ApotheCom, San Francisco, CA, USA), and was funded by F. Hoffmann-La Roche Ltd.
Legal entity responsible for the study
F. Hoffmann-La Roche Ltd.
Funding
F. Hoffmann-La Roche Ltd.
Disclosure
K. Lewis: Financial Interests, Personal, Other, Honoraria: Array BioPharma, Iovance Biotherapeutics; Financial Interests, Personal, Advisory Board: Array BioPharma, Merck, Roche, Regeneron, Sanofi, Iovance Biotherapeutics, Nektar; Financial Interests, Institutional, Research Grant: Roche/Genentech, Merck, Array BioPharma, Incyte, Nektar, Iovance Biotherapeutics, Bristol Myers Squibb, Kartos Therapeutics, OncoSec, Regeneron, Alkermes, Neon Therapeutics, Ultimovacs, SenhwaBiosciences, Replimune, Amgen, Seattle Genetics; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Merck, Roche/Genentech, Neon Therapeutics, Alkermes; Financial Interests, Personal, Officer, Travel, Accommodations, Expenses: Regeneron; Non-Financial Interests, Personal, Advisory Board: Roche/Genentech, Regeneron. C. Robert: Financial Interests, Personal, Advisory Board: BMS, Roche, Pierre Fabre, Novartis, Sanofi, MSD, AstraZeneca, Pfizer; Financial Interests, Personal, Stocks/Shares: Ribonexus; Financial Interests, Institutional, Research Grant: Novartis, Phio Pharmaeutical. R. Ramella Munhoz: Financial Interests, Personal, Other, Honoraria: BMS, MSD, Novartis, Sanofi, Merck Serono, Bayer, Daiichi Sankyo; Financial Interests, Personal, Speaker’s Bureau: BMS, MSD, Novartis, Sanofi; Financial Interests, Personal, Funding: Roche, BMS, Novartis, MSD, Bayer; Financial Interests, Personal, Other, Travel, Accomodations, Expenses: BMS; Financial Interests, Personal, Other, Consulting: Sanofi, BMS, MSD, Daiichi Sankyo. G. Liszkay: Financial Interests, Personal, Research Grant: Clinical excellence program, Establishment of the National Tumorbiology Laboratory, Investment of the Future; Financial Interests, Personal, Other, Consulting: Roche, MSD, Novartis, BMS, Pfizer, Sanofi; Financial Interests, Personal, Other, Honoria: Roche, MSD, Novartis, BMS; Financial Interests, Personal, Advisory Board: Roche, MSD, Novartis, BMS, Pfizer, Sanofi; Financial Interests, Personal, Advisory Role: College of Dermatology Medical Research Council, CEEAO; Financial Interests, Personal, Other, Honoraria: Pfizer, Sanofi; Financial Interests, Institutional, Research Grant: Roche. L. de la Cruz Merino: Financial Interests, Personal, Research Grant: Roche, Celgene, MSD; Financial Interests, Personal, Advisory Role: BMS, MSD, Roche, Novartis, Gilead, Incyte. J. Olah: Financial Interests, Personal, Advisory Role: Roche, Novartis, BMS, Sanofi, MSD. P. Queirolo: Financial Interests, Personal, Advisory Role: Novartis, Roche, Pierre Fabre, MSD, BMS, Merck, Sanofi, Sun Pharma; Financial Interests, Personal, Speaker’s Bureau: Novartis, Roche, Pierre Fabre, MSD, BMS, Merck, Sanofi, Sun Pharma; Financial Interests, Personal, Other, Travel, Accommodation, Expenses: Sanofi, MSD. J. Mackiewicz: Financial Interests, Personal, Advisory Role: BMS, MSD; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: BMS, MSD, Pierre Fabre; Financial Interests, Personal, Speaker’s Bureau: BMS, MSD, Novartis; Financial Interests, Personal, Advisory Board: Pierre Fabre. H. Li: Financial Interests, Personal, Full or part-time Employment: Roche. Q. Zhu: Financial Interests, Personal, Full or part-time Employment: Genentech. C. Hertig: Financial Interests, Personal, Full or part-time Employment: Roche. N. Paranthaman: Financial Interests, Personal, Full or part-time Employment: Genentech; Financial Interests, Personal, Stocks/Shares: Genentech. E.F. McKenna: Financial Interests, Personal, Stocks/Shares: Genentech. R. Gutzmer: Financial Interests, Personal, Advisory Role: Roche, BMS, MSD, Novartis, Amgen, Merck Serono, Almirall, SUN, Sanofi, Pierre-Fabre, 4SC, Immunocore; Financial Interests, Personal, Principal Investigator: J & J, Amgen, Merck Serono, Sanofi, Kyowa-Kirin, Almirall; Financial Interests, Institutional, Research Grant: BMS, Sanofi, SUN, IO Biotech, Pfizer, Novartis, Merck Serono, Pierre-Fabre, MSD; Non-Financial Interests, Personal, Other, Head of the DeCOG/ADO: DeCOG/ADO; Financial Interests, Personal, Other, Travel support for meeting participation: Roche, BMS, SUN, Merck Serono, Pierre-Fabre. G. McArthur: Financial Interests, Institutional, Research Grant: Genentech/Roche, MSD, Roche. P.A. Ascierto: Financial Interests, Personal, Other, Consultant and Advisory Role: BMS, Roche Genentech, MSD, Novartis, Pfizer/Array, Merck Serono, Pierre Fabre, AstraZeneca, Sun Pharma, Sanofi, Idera, Sandoz, Immunocore, 4SC, Nektar, Boehringer Ingelheim, Regeneron; Financial Interests, Personal, Other, Consultant Role: Italfarmaco; Financial Interests, Personal, Other, Advisory Role: Eisai, Seagen; Financial Interests, Personal, Other, Consultant Role: Daiichi Sankyo, Pfizer, Oncosec, Nouscom, Lunaphore; Financial Interests, Personal, Other, Consultant role: Medicenna, Bio-AI Health; Financial Interests, Institutional, Funding, Clinical trial and translational research: BMS; Financial Interests, Institutional, Funding, Clinical Trial: Roche Genentech, Pfizer/Array, Sanofi; Non-Financial Interests, Leadership Role, President since 2010: Fondazione Melanoma Onlus Italy; Non-Financial Interests, Leadership Role, President since 2014: Campania Society of ImmunoTherapy of Cancer (SCITO) Italy; Non-Financial Interests, Other, Member of Steering Committee since 2016: Society for Melanoma Research (SMR); Non-Financial Interests, Invited Speaker, November 2017 - December 2021: Society for Immunotherapy of Cancer (SITC); Non-Financial Interests, Member: ASCO, SITC, EORTC Melanoma Cooperative Group, AIOM, SMR; Other, Travel Support: MSD.