Abstract
Background: Nivolumab has been widely studied in non-acral cutaneous melanoma; however, limited data are available in other melanoma subtypes. We report outcomes by melanoma subtype in patients who received nivolumab after progression on prior ipilimumab. Patients and methods: CheckMate 172 was a phase II, single-arm, open-label, multicentre study that evaluated nivolumab in patients with advanced melanoma who progressed on or after ipilimumab. Patients received 3 mg/kg of nivolumab, every 2 weeks for up to 2 years. The primary end-point was incidence of grade ≥3, treatment-related select adverse events (AEs). Results: Among 1008 treated patients, we report data on patients with non-acral cutaneous melanoma (n = 723 [71.7%]), ocular melanoma (n = 103 [10.2%]), mucosal melanoma (n = 63 [6.3%]), acral cutaneous melanoma (n = 55 [5.5%]) and other melanoma subtypes (n = 64 [6.3%]). There were no meaningful differences in the incidence of grade ≥3, treatment-related select AEs among melanoma subtypes or compared with the total population. No new safety signals emerged. At a minimum follow-up of 18 months, median overall survival was 25.3 months for non-acral cutaneous melanoma and 25.8 months for acral cutaneous melanoma, with 18-month overall survival rates of 57.5% and 59.0%, respectively. Median overall survival was 12.6 months for ocular melanoma and 11.5 months for mucosal melanoma, with 18-month overall survival rates of 34.8% and 31.5%, respectively. Conclusions: The safety profile of nivolumab after ipilimumab is similar across melanoma subtypes. Compared with non-acral cutaneous melanoma, patients with acral cutaneous melanoma had similar survival outcomes, whereas those with ocular and mucosal melanoma had lower median overall survival. ClinicalTrials.gov ID: : NCT02156804.
| Original language | English |
|---|---|
| Journal | European Journal of Cancer |
| Volume | 119 |
| Pages (from-to) | 168-178 |
| Number of pages | 11 |
| ISSN | 0959-8049 |
| DOIs | |
| Publication status | Published - 09.2019 |
Funding
This work was supported by Bristol-Myers Squibb (Princeton, NJ, USA). P.N. has received personal fees from Bristol-Myers Squibb for participation in trial steering committees and advisory boards and has received fees for advisory boards or speaker′s bureau from AstraZeneca, Immunocore, Ipsen, Merck, MSD, Novartis, Pfizer, Pierre Fabre and Roche. P.A.A. declares a consulting or advisory role for Bristol-Myers Squibb, Roche-Genentech, MSD, Array, Novartis, Merck Serono, Pierre Fabre, Incyte, Genmab, NewLink Genetics, MedImmune, AstraZeneca, Syndax Pharmaceuticals, Sun Pharmaceuticals, Sanofi, Idera, Ultimovacs, Sandoz and Immunocore; has received research funds from Bristol-Myers Squibb and Array and has received travel support from MSD. J.H. has received grants from Bristol-Myers Squibb, Novartis, MSD and Neon Therapeutics for research performed at his institution and has received financial compensation paid to his institution from AstraZeneca, Celsius Therapeutics, Bayer, Bristol-Myers Squibb, MSD, Merck Serono, Pfizer, GSK, Neon Therapeutics, Immunocore, Seattle Genetics, Roche/Genentech and Gadeta for serving as an advisor. E.E. has received personal fees from Bristol-Myers Squibb for participation in advisory boards. L.D. has received grants from Novartis for research performed at his institution; has received personal fees from Novartis, Bristol-Myers Squibb, MSD and BIOCAD for travel and accommodations during congresses and has received personal fees from Roche, Bristol-Myers Squibb and BIOCAD for participation in advisory boards. C.G. has received grants and personal fees from Bristol-Myers Squibb, Novartis, Roche and Sanofi for participation in advisory boards; has also received personal fees from Amgen, MSD and Pierre Fabre for participation in advisory boards and has received grants and personal fees from NeraCare and personal fees from Philogen for serving as an advisor. M.G. has received grants from Bristol-Myers Squibb, MSD and Novartis for participating in advisory boards. P.L. has received personal fees from Bristol-Myers Squibb and GSK for consulting, lectures and clinical trials; has received personal fees from Merck and Chugai for consulting and lectures and has received personal fees from Novartis and Amgen for consulting and clinical trials. V.C.-S. has received personal fees from Bristol-Myers Squibb, MSD, Novartis, Pierre Fabre and Merck Serono for participation in advisory boards. H.G. has received grants from Bristol-Myers Squibb, Roche, MSD and Novartis for research performed at her institution; has received personal fees from Bristol-Myers Squibb, Roche and Amgen for participation in advisory boards and for travel and accommodations and has received personal fees from MSD, Novartis and Pierre Fabre for participation in advisory boards. M.M. has received patients′ fees paid to his institution from Bristol-Myers Squibb, MSD, AstraZeneca, Roche and Merck and has received personal fees from MSD, AstraZeneca, Roche and Merck for participation in advisory boards. M.T.F. has received personal fees from Pierre Fabre and Novartis for participation in advisory boards and has received travel expenses from Bristol-Myers Squibb. C.H. has received personal fees from Amgen, Bristol-Myers Squibb, MSD, Novartis, Pierre Fabre and Roche for participation in advisory boards and lectures. P.T. has received personal fees for consulting, honoraria for lectures and travel expenses from Bristol-Myers Squibb and Pierre Fabre; has received personal fees for consulting and honoraria for lectures from Novartis and Roche; has received personal fees for consulting and travel expenses from Merck Serono; has received personal fees and honoraria for lectures from CureVac and has received personal fees for consulting from Sanofi. R.G. has received personal fees and non-financial support from Bristol-Myers Squibb, Roche, Merck Serono and Pierre Fabre, as well as meeting support and honoraria for lectures and advice; has received grants, personal fees, non-financial support and honoraria for lectures and advice from Amgen and Novartis; has received personal fees, non-financial support and honoraria for lectures and advice from Sanofi-Regeneron and Almirall Hermal and has received personal fees and honoraria from MSD and Sun Pharmaceuticals for lectures and advice. He has received grants, personal fees and honoraria from Pfizer for lectures and advice; has received personal fees and honoraria from LEO and 4SC for advice; has received personal fees and honoraria from AstraZeneca for lectures and has received grants from Johnson & Johnson. T.K.G. has no conflicts of interest to disclose. D.B. has received personal fees from Bristol-Myers Squibb, MSD and Roche for participation in advisory boards. P.R. has received personal fees and honoraria for lectures and advisory boards from Bristol-Myers Squibb, Novartis and MSD; has received personal fees and honoraria for lectures from Roche, Pfizer, Eli Lilly and Pierre Fabre and has received personal fees and honoraria for advisory boards from Blueprint Medicines. R.P. has received personal fees and speaker honoraria from Bristol-Myers Squibb; has received fees paid to her institution for clinical trial delivery from Bristol-Myers Squibb; has received honoraria for advisory boards from Pierre Faber, Genmab, Bayer, Octimet, Clovis Oncology, Novartis, Karus Therapeutics, Biosceptre, Cybrexa, Ellipses and Sanofi Aventis; has been paid for delivery of educational talks or chairing educational meetings by AstraZeneca, Novartis, Bayer and Tesaro and has received funds to support attendance at conferences from Bristol-Myers Squibb and MSD. A.W. has received grants for clinical trial support from Bristol-Myers Squibb; has received travel grants from Bristol-Myers Squibb and personal fees for lectures and for participation in advisory boards and has received travel grants and personal fees for lectures from Novartis and MSD. M.K. has received grants for study fees from Bristol-Myers Squibb, Novartis, Roche, MSD, Sun Pharmaceutical and Sanofi and personal fees for participation in advisory boards. M.M. has received grants for research from Novartis and Roche and has received personal fees from Bristol-Myers Squibb, Novartis, Pierre Fabre and Roche for participation in advisory boards. I.M.-R. has received personal fees from Bristol-Myers Squibb, MSD, Novartis, Roche, Pierre Fabre, Amgen, AstraZeneca, Incyte, Merck Serono, Regeneron, Sanofi and Bioncotech for participation in advisory boards. E.M.-C. has no conflicts of interest to disclose. R.D. discloses intermittent, project-focused consulting and/or advisory relationships with Novartis, MSD, Bristol-Myers Squibb, Roche, Amgen, Takeda, Pierre Fabre, Sun Pharmaceutical and Sanofi outside the submitted work. E.G. is an employee of Bristol-Myers Squibb. T.C.Y. is an employee of Bristol-Myers Squibb. D.S. has received grants, personal fees and non-financial support from Bristol-Myers Squibb and Novartis for participation in advisory boards; has received speaker honoraria and patients′ fees paid to his institution from Bristol-Myers Squibb and Novartis; has received personal fees and non-financial support from Roche, MSD/Merck, Amgen, Merck-EMD, Pierre Fabre, Philogen and Incyte for participation in advisory boards; has received speaker honoraria and patients′ fees paid to his institution from Roche, MSD/Merck, Amgen, Merck-EMD, Pierre Fabre, Philogen and Incyte; has received non-financial support and patients′ fees paid to his institution from Regeneron; has received speaker′s honoraria and personal fees for participation in advisory boards from Sanofi; has received personal fees and non-financial support for participation in advisory boards and patients′ fees paid to his institution from 4SC and has received personal fees from Array and Pfizer for participation in advisory boards. The authors thank the patients and families who made this study possible and the investigators and the clinical study teams who participated in this study. The authors also acknowledge ONO Pharmaceutical Company, Ltd. (Osaka, Japan), for contributions to nivolumab development. Professional medical writing and editorial assistance were provided by Jennifer DiNieri, PhD, and Cara Hunsberger, MS, at StemScientific, an Ashfield Company, funded by Bristol-Myers Squibb . The authors were fully responsible for all content within this manuscript.
Research Areas and Centers
- Academic Focus: Center for Infection and Inflammation Research (ZIEL)
