Nivolumab plus Ipilimumab in Microsatellite-Instability-High Metastatic Colorectal Cancer
Por:
Andre, T, Elez, E, Van Cutsem, E, Jensen, LH, Bennouna, J, Mendez, G, Schenker, M, de la Fouchardiere, C, Limon, ML, Yoshino, T, Li, J, Lenz, HJ, Mozo, JLM, Tortora, G, Garcia-Carbonero, R, Dahan, L, Chalabi, M, Joshi, R, Goekkurt, E, Braghiroli, MI, Cil, T, Cela, E, Chen, T, Lei, M, Dixon, M, Abdullaev, S and Lonardi, S
Publicada:
28 nov 2024
Resumen:
Patients with microsatellite-instability-high (MSI-H) or mismatch-repair-deficient (dMMR) metastatic colorectal cancer have poor outcomes with standard chemotherapy with or without targeted therapies. Nivolumab plus ipilimumab has shown clinical benefit in nonrandomized studies of MSI-H or dMMR metastatic colorectal cancer. METHODS In this phase 3 open-label trial, we randomly assigned patients with unresectable or metastatic colorectal cancer and MSI-H or dMMR status according to local testing to receive, in a 2:2:1 ratio, nivolumab plus ipilimumab, nivolumab alone, or chemotherapy with or without targeted therapies. The dual primary end points, assessed in patients with centrally confirmed MSI-H or dMMR status, were progression-free survival with nivolumab plus ipilimumab as compared with chemotherapy as first- line therapy and progression-free survival with nivolumab plus ipilimumab as compared with nivolumab alone in patients regardless of previous systemic treatment for metastatic disease. At this prespecified interim analysis, the first primary end point (involving nivolumab plus ipilimumab vs. chemotherapy) was assessed. RESULTS A total of 303 patients who had not previously received systemic treatment for metastatic disease were randomly assigned to receive nivolumab plus ipilimumab or chemotherapy; 255 patients had centrally confirmed MSI-H or dMMR tumors. At a median follow-up of 31.5 months (range, 6.1 to 48.4), progression-free survival outcomes (the primary analysis) were significantly better with nivolumab plus ipilimumab than with chemotherapy (P<0.001 for the between-group difference in progression-free survival, calculated with the use of a two-sided stratified log-rank test); 24-month progression-free survival was 72% (95% confidence interval [CI], 64 to 79) with nivolumab plus ipilimumab as compared with 14% (95% CI, 6 to 25) with chemotherapy. At 24 months, the restricted mean survival time was 10.6 months (95% CI, 8.4 to 12.9) longer with nivolumab plus ipilimumab than with chemotherapy, a finding consistent with the primary analysis of progression-free survival. Grade 3 or 4 treatment-related adverse events occurred in 23% of the patients in the nivolumab-plusipilimumab group and in 48% of the patients in the chemotherapy group. CONCLUSIONS Progression-free survival was longer with nivolumab plus ipilimumab than with chemotherapy among patients who had not previously received systemic treatment for MSI-H or dMMR metastatic colorectal cancer. (Funded by Bristol Myers Squibb and Ono Pharmaceutical; CheckMate 8HW ClinicalTrials.gov number, NCT04008030.)
Filiaciones:
Andre, T:
Sorbonne Univ, Hop St Antoine, Assistance Publ Hop Paris, Unite Mixte Rech Sci 938, Paris, France
SIRIC CURAMUS, Paris, France
Elez, E:
Univ Autonoma Barcelona, Vall dHebron Univ Hosp & Inst Oncol VHIO, Barcelona, Spain
Van Cutsem, E:
Univ Hosp Gasthuisberg, Leuven, Belgium
Univ Leuven, KU Leuven, Leuven, Belgium
Jensen, LH:
Univ Hosp Southern Denmark, Vejle Hosp, Vejle, Denmark
Bennouna, J:
Hop Foch, Suresne, France
Mendez, G:
Hosp Univ Fdn Favaloro, Buenos Aires, Argentina
Schenker, M:
Centrul Oncol Sf Nectarie, Craiova, Romania
de la Fouchardiere, C:
Aix Marseille Univ, Inst Paoli Calmettes, Marseille, France
Limon, ML:
Hosp Univ Virgen Rocio, Seville, France
Yoshino, T:
Natl Canc Ctr Hosp East, Chiba, Japan
Li, J:
Shanghai East Hosp, Shanghai, Peoples R China
Lenz, HJ:
Univ Southern Calif, Norris Comprehens Canc Ctr, Los Angeles, CA USA
:
Hosp Univ Germans Trias i Pujol, Inst Catala Oncol, Badalona, Spain
Tortora, G:
Fdn Policlin Univ A Gemelli IRCCS, Rome, Italy
Garcia-Carbonero, R:
Hosp Univ 12 Octubre, Med Dept UCM, Imas12, Madrid, Spain
Dahan, L:
Aix Marseille Univ, La Timone, Marseille, France
Chalabi, M:
Netherlands Canc Inst, Amsterdam, Netherlands
Joshi, R:
Canc Res SA, Adelaide, SA, Australia
Goekkurt, E:
Hematol Oncol Practice Eppendorf HOPE, Hamburg, Germany
Univ Canc Ctr Hamburg UCCH, Hamburg, Germany
Braghiroli, MI:
Inst Canc Sao Paulo, Sao Paulo, Brazil
Cil, T:
Adana City Educ & Res Hosp, Adana, Turkiye
Cela, E:
Bristol Myers Squibb, Princeton, NJ USA
Chen, T:
Bristol Myers Squibb, Princeton, NJ USA
Lei, M:
Bristol Myers Squibb, Princeton, NJ USA
Dixon, M:
Bristol Myers Squibb, Princeton, NJ USA
Abdullaev, S:
Bristol Myers Squibb, Princeton, NJ USA
Lonardi, S:
Veneto Inst Oncol IOV IRCCS, Padua, Italy
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