TY - JOUR
T1 - Adjuvant nivolumab versus ipilimumab (CheckMate 238 trial)
T2 - Reassessment of 4-year efficacy outcomes in patients with stage III melanoma per AJCC-8 staging criteria
AU - Larkin, James
AU - Weber, Jeffrey
AU - Del Vecchio, Michele
AU - Gogas, Helen
AU - Arance, Ana M.
AU - Dalle, Stephane
AU - Cowey, C. Lance
AU - Schenker, Michael
AU - Grob, Jean Jacques
AU - Chiarion-Sileni, Vanna
AU - Márquez-Rodas, Iván
AU - Butler, Marcus O.
AU - Di Giacomo, Anna Marie
AU - Middleton, Mark R.
AU - De la Cruz-Merino, Luis
AU - Arenberger, Petr
AU - Atkinson, Victoria
AU - Hill, Andrew
AU - Fecher, Leslie A.
AU - Millward, Michael
AU - Khushalani, Nikhil I.
AU - Queirolo, Paola
AU - Long, Georgina V.
AU - Lobo, Maurice
AU - Askelson, Margarita
AU - Ascierto, Paolo A.
AU - Mandalá, Mario
N1 - Funding Information:
This study was sponsored by Bristol Myers Squibb and Ono Pharmaceutical .
Funding Information:
MS has received research/grant support from AbbVie , Amgen, Astellas , AstraZeneca , Bayer , BMS, BeiGene , Bioven , Clovis Pharmaceutical , Daiichi Sankyo , Eli Lilly , Gilead , GSK , Merck Serono , MSD, Mylan , Novartis, Pfizer, Regeneron, Roche, Sanofi , and Tesaro .
Funding Information:
This study was sponsored by Bristol Myers Squibb and Ono Pharmaceutical.The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: JLa has worked in a consulting/advisory role for iOnctura, Apple Tree, Merck, Bristol Myers Squibb (BMS), Eisai, Debipharm, and Incyte; has received honoraria from AstraZeneca, BMS, Eisai, EUSA Pharma, GlaxoSmithKline (GSK), Incyte, Ipsen, Merck, touchEXPERTS, Royal College of Physicians, Cambridge Healthcare Research, Royal College of General Practitioners, VJOncology, Agence Unik, Merck Sharp & Dohme (MSD), Novartis, Aptitude, Pierre Fabre, Pfizer, Roche, Seagen, Inselgruppe, eCancer, Ultimovacs, Calithera, and Goldman Sachs; and has received research/grant support from Achilles Therapeutics, BMS, Immunocore, Aveo, Pharmacyclics, MSD, Nektar Therapeutics, Covance, Novartis, Pfizer, and Roche.HG has worked in a consulting/advisory role for Amgen, BMS, MSD, and Replimune; has received honoraria from BMS, MSD, Novartis, Sanofi, and Pierre Fabre; and has received research/grant support from Amgen, BMS, Iovance, MSD, Pfizer, and Replimune.MS has received research/grant support from AbbVie, Amgen, Astellas, AstraZeneca, Bayer, BMS, BeiGene, Bioven, Clovis Pharmaceutical, Daiichi Sankyo, Eli Lilly, Gilead, GSK, Merck Serono, MSD, Mylan, Novartis, Pfizer, Regeneron, Roche, Sanofi, and Tesaro.VC-S has received honoraria from Pierre Fabre, Novartis, and BMS; and has received travel/congress support from Novartis and Pierre Fabre.IM-R has worked in a consulting/advisory role for AstraZeneca, Amgen, BMS, Incyte, Merck Serono, MSD, Novartis, Pierre Fabre, Roche, Sun Pharma, Highlight Therapeutics, Regeneron, and Sanofi; has received honoraria from BMS, MSD, Roche, Pierre Fabre, Novartis, and Sun Pharma; and has received travel/congress support from BMS, MSD, Novartis, Pierre Fabre, Roche, and Sun Pharma.MOB has worked in a consulting/advisory role for BMS, GSK, Immunocore, Merck, Novartis, Pfizer, Adaptimmune, Sun Pharma, Instil Bio, IOVANCE, Medison, LaRoche Possey, and Sanofi; has received research/grant support from Merck, Takara Bio, and Novartis; has received honoraria from Sanofi, BMS, Merck, and Novartis; and has served on the safety review board for Adaptimmune, and GSK.MRM has worked in a consulting/advisory role for Novartis, BioLineRx, BMS, Immunocore, Kineta, Merck, and Silicon Therapeutics; and has received institutional research/grant support from Roche, Astrazeneca, GSK, Immunocore, BioLineRx, Pfizer, Regeneron, Replimune, and GRAIL.LAF has worked in a consulting/advisory role for Elsevier, and Via Oncology; has received cooperative group research/grant support from Array BioPharma and Pfizer; has received institutional research/grant support from Array BioPharma, BMS, EMD Serono, Incyte, Kartos Therapeutics, Merck, and Pfizer; has received honoraria from ASCO, and the Michigan Society of Hematology and Oncology; and has served on the data and safety monitoring board of the Hoosier Cancer Research Network.NIK has received institutional research/grant support from Amgen, BMS, Celgene, GSK, HUYA Bioscience, Merck, Novartis, Regeneron, and Replimune; had received honoraria from Novartis and Replimune; holds stock in Amarin, Asensus, Bellicum, and Mazor Robotics; has served on the data and safety monitoring or advisory board of AstraZeneca, BMS, Castle Biosciences, Genzyme, Incyte, Instil Bio, Iovance, Merck, NCCN, Nektar Therapeutics, Novartis, and Regeneron; and has served in a leadership position for BMS, NCCN, Nektar Therapeutics, Regeneron, and Replimune.PAA has worked in a consulting/advisory role for Array BioPharma, AstraZeneca, Boehringer Ingelheim, BMS, Idera Pharmaceuticals, Immunocore, Italfarmaco, Nektar, Pfizer, Lunaphore, Medicenna, Bio-AI Health, Eisai, Regeneron, Daiichi Sankyo, Oncosec, Nouscom, Seagen, iTeos, 4SC, MSD, Merck Serono, Novartis, Pierre Fabre, Roche/Genentech, Sandoz, Sanofi, and Sun Pharma; and has received research/grant support from Array BioPharma, Pfizer, BMS, Sanofi, and Roche/Genentech.
Publisher Copyright:
© 2022 The Author(s)
PY - 2022/9
Y1 - 2022/9
N2 - Purpose: Nivolumab was approved as adjuvant therapy for melanoma based on data from CheckMate 238, which enrolled patients per American Joint Committee on Cancer version 7 (AJCC-7) criteria. Here, we analyse long-term outcomes per AJCC-8 staging criteria compared with AJCC-7 results to inform clinical decisions for patients diagnosed per AJCC-8. Patients and methods: In a double-blind, phase 3 trial (NCT02388906), patients aged ≥15 years with resected, histologically confirmed AJCC-7 stage IIIB, IIIC, or IV melanoma were randomised to receive nivolumab 3 mg/kg every 2 weeks or ipilimumab 10 mg/kg every 3 weeks for 4 doses and then every 12 weeks, both intravenously ≤1 year. Recurrence-free survival (RFS) and distant metastasis-free survival (DMFS) were assessed in patients with stage III disease, per AJCC-7 and AJCC-8. Results: Per AJCC-7 staging, 42.4% and 57.3% of patients were in substage IIIB and IIIC, respectively; per AJCC-8, 1.1%, 30.4%, 62.8%, and 5.0% were in IIIA, IIIB, IIIC, and IIID. After 4 years' minimum follow-up, the AJCC-7 superior efficacy of nivolumab over ipilimumab in patients with resected stage III melanoma was preserved per AJCC-8 analysis. No statistically significant difference in RFS between stage III substage hazard ratios was observed per AJCC-7 or -8 staging criteria (interaction test: AJCC-7, P = 0.8115; AJCC-8, P = 0.1051; P = 0.8392 ((AJCC-7) and P = 0.8678 (AJCC-8) for DMFS). Conclusions: CheckMate 238 4-year RFS and DMFS outcomes are consistent per AJCC-7 and AJCC-8 staging criteria. Outcome benefits can therefore be translated for patients diagnosed per AJCC-8.
AB - Purpose: Nivolumab was approved as adjuvant therapy for melanoma based on data from CheckMate 238, which enrolled patients per American Joint Committee on Cancer version 7 (AJCC-7) criteria. Here, we analyse long-term outcomes per AJCC-8 staging criteria compared with AJCC-7 results to inform clinical decisions for patients diagnosed per AJCC-8. Patients and methods: In a double-blind, phase 3 trial (NCT02388906), patients aged ≥15 years with resected, histologically confirmed AJCC-7 stage IIIB, IIIC, or IV melanoma were randomised to receive nivolumab 3 mg/kg every 2 weeks or ipilimumab 10 mg/kg every 3 weeks for 4 doses and then every 12 weeks, both intravenously ≤1 year. Recurrence-free survival (RFS) and distant metastasis-free survival (DMFS) were assessed in patients with stage III disease, per AJCC-7 and AJCC-8. Results: Per AJCC-7 staging, 42.4% and 57.3% of patients were in substage IIIB and IIIC, respectively; per AJCC-8, 1.1%, 30.4%, 62.8%, and 5.0% were in IIIA, IIIB, IIIC, and IIID. After 4 years' minimum follow-up, the AJCC-7 superior efficacy of nivolumab over ipilimumab in patients with resected stage III melanoma was preserved per AJCC-8 analysis. No statistically significant difference in RFS between stage III substage hazard ratios was observed per AJCC-7 or -8 staging criteria (interaction test: AJCC-7, P = 0.8115; AJCC-8, P = 0.1051; P = 0.8392 ((AJCC-7) and P = 0.8678 (AJCC-8) for DMFS). Conclusions: CheckMate 238 4-year RFS and DMFS outcomes are consistent per AJCC-7 and AJCC-8 staging criteria. Outcome benefits can therefore be translated for patients diagnosed per AJCC-8.
KW - AJCC-8 criteria
KW - Distant metastases
KW - Ipilimumab
KW - Melanoma adjuvant therapy
KW - Nivolumab
KW - Recurrence-free survival
KW - Stage 3
UR - https://www.scopus.com/pages/publications/85135858543
U2 - 10.1016/j.ejca.2022.06.041
DO - 10.1016/j.ejca.2022.06.041
M3 - Article
C2 - 35964471
AN - SCOPUS:85135858543
SN - 0959-8049
VL - 173
SP - 285
EP - 296
JO - European Journal of Cancer
JF - European Journal of Cancer
ER -
