Abstract
Background: Ipilimumab has shown long-term overall survival (OS) in patients with advanced melanoma in clinical trials, but robust real-world evidence is lacking. We present long-term outcomes from the IMAGE study (NCT01511913) in patients receiving ipilimumab and/or non-ipilimumab (any approved treatment other than ipilimumab) systemic therapies. Methods: IMAGE was a multinational, prospective, observational study assessing adult patients with advanced melanoma treated with ipilimumab or non-ipilimumab systemic therapies between June 2012 and March 2015 with ≥3 years of follow-up. Adjusted OS curves based on multivariate Cox regression models included covariate effects. Safety and patient-reported outcomes were assessed. Results: Among 1356 patients, 1094 (81%) received ipilimumab and 262 (19%) received non-ipilimumab index therapy (systemic therapy [chemotherapy, anti–programmed death 1 antibodies, or BRAF ± MEK inhibitors], radiotherapy, and radiosurgery). In the overall population, median age was 64 years, 60% were male, 78% were from Europe, and 78% had received previous treatment for advanced melanoma. In the ipilimumab-treated cohort, 780 (71%) patients did not receive subsequent therapy (IPI-noOther) and 314 (29%) received subsequent non-ipilimumab therapy (IPI-Other) on study. In the non-ipilimumab–treated cohort, 205 (78%) patients remained on or received other subsequent non-ipilimumab therapy (Other-Other) and 57 (22%) received subsequent ipilimumab therapy (Other-IPI) on study. Among 1151 patients who received ipilimumab at any time during the study (IPI-noOther, IPI-Other, and Other-IPI), 296 (26%) reported CTCAE grade ≥ 3 treatment-related adverse events, most occurring in year 1. Ipilimumab-treated and non-ipilimumab–treated patients who switched therapy (IPI-Other and Other-IPI) had longer OS than those who did not switch (IPI-noOther and Other-Other). Patients with prior therapy who did not switch therapy (IPI-noOther and Other-Other) showed similar OS. In treatment-naive patients, those in the IPI-noOther group tended to have longer OS than those in the Other-Other group. Patient-reported outcomes were similar between treatment cohorts. Conclusions: With long-term follow-up (≥ 3 years), safety and OS in this real-world population of patients treated with ipilimumab 3 mg/kg were consistent with those reported in clinical trials. Patient-reported quality of life was maintained over the study period. OS analysis across both pretreated and treatment-naive patients suggested a beneficial role of ipilimumab early in treatment. Trial registration: ClinicalTrials.gov, NCT01511913. Registered January 19, 2012 – Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT01511913
| Original language | English |
|---|---|
| Article number | 642 |
| Journal | BMC Cancer |
| Volume | 21 |
| Issue number | 1 |
| Pages (from-to) | 642 |
| ISSN | 1471-2407 |
| DOIs | |
| Publication status | Published - 12.2021 |
Funding
This study was supported by Bristol Myers Squibb (no grant number is applicable). The sponsor and authors participated in the design of the study, data analysis, and interpretation of data. We would like to thank the patients and families who made this study possible and the clinical study teams who participated in the study. We would like to acknowledge Dr. Amy Abernethy?s contributions as a co-chair of the scientific advisory committee for the IMAGE study. Dr. Abernethy?s contribution occurred prior to her appointment as a Principal Deputy Commissioner of the Food and Drug Administration. The views expressed are those of the authors and not necessarily those of the Food and Drug Administration or the US government. All authors contributed to and approved the presentation; writing and editorial assistance were provided by Kakoli Parai, PhD, and Andrea Lockett of Ashfield MedComms, an Ashfield Health Company, funded by Bristol Myers Squibb. SD has received institutional research grants from Bristol Myers Squibb and Merck Sharp & Dohme, and travel support from Bristol Myers Squibb. LM has received personal fees for French Medical Board expenses and congress travel support from Bristol Myers Squibb and Roche. PC has served on advisory boards, received speaker fees, and received institutional research support from Bristol Myers Squibb, Merck Sharp & Dohme, and Novartis. ML declares no conflicts to disclose. RB reports personal fees from Bristol Myers Squibb. AMA has served as an advisor, consultant, and speaker for Amgen, Bristol Myers Squibb, Merck Sharp & Dohme, Novartis, Pierre Fabre, Roche, and Sanofi. FM has served as an advisor to Bristol Myers Squibb, Novartis, Pierre Fabre, Roche, and Sanofi-Aventis; has served as a speaker for Merck Sharp & Dohme; and has received travel support from Bristol Myers Squibb, Novartis, Pierre Fabre, Roche, and Sanofi-Aventis. PT has worked as a consultant to Bristol Myers Squibb, Merck Serono, Novartis, Pierre Fabre, Roche, and Sanofi; has served as a speaker for Bristol Myers Squibb, CureVac, Merck Sharp & Dohme, Novartis, Pierre Fabre, and Roche; and has received travel support from Bristol Myers Squibb, and Pierre Fabre. RG has worked as an advisor to Almitall Hermal, Amgen, Bristol Myers Squibb, 4SC, Merck Serono, Merck Sharp & Dohme, Novartis, Pierre Fabre, Pfizer, Sanofi Regeneron, Sun Pharma, and Roche; has served as a speaker for Almitall Hermal, Amgen, Bristol Myers Squibb, Merck Serono, Merck Sharp & Dohme, Novartis, Pierre Fabre, Pfizer, Sanofi Regeneron, Sun Pharma, and Roche; has received meeting support from Bristol Myers Squibb, Merck Serono, Pierre Fabre, and Roche; and has received institutional research support from Bristol Myers Squibb. BB and KO are employees of Syneos Health, the contract research organisation that conducted the study including data collection and statistical analysis, but were not compensated for authorship. JB was an employee of Bristol Myers Squibb at the time of this study. TKL is an employee of Bristol Myers Squibb. SDM declares no conflicts to disclose. JS and SK are employees of Bristol Myers Squibb. JL and AM are employees of and stockholders in Bristol Myers Squibb. MRM has served as an advisor to Amgen, Array Biopharma, BiolineRx, Bristol Myers Squibb, GlaxoSmithKline, Immunocore, Kineta, Novartis, Rigontec, and Silicon Therapeutics; has received institutional research support from Array Biopharma, AstraZeneca, BiolineRx, Bristol Myers Squibb, Eisai, GlaxoSmithKline, Immunocore, Merck, Merck Sharp & Dohme, Millennium, Novartis, Pfizer, Regeneron, Replimune, Rigontec, and Roche; has received travel support from Immunocore, Merck, Merck Sharp & Dohme, and Replimune; and is a member of the Independent Data Safety Monitoring Committee for Eisai and Merck/Merck Sharp & Dohme.
