LBA2_PR - Ipilimumab (IPI) vs placebo (PBO) after complete resection of stage III melanoma: final overall survival results from the EORTC 18071 randomized, d...

Date 08 October 2016
Event ESMO 2016 Congress
Session Presidential Symposium 1
Topics Melanoma and other Skin Tumours
Presenter Alexander Eggermont
Citation Annals of Oncology (2016) 27 (6): 1-36. 10.1093/annonc/mdw435
Authors A.M. Eggermont1, V. Chiarion-Sileni2, J. Grob3, R. Dummer4, J.D. Wolchok5, H. Schmidt6, O. Hamid7, C. Robert8, P.A. Ascierto9, J.M. Richards10, C. Lebbé11, V. Ferraresi12, M. Smylie13, J.S. Weber14, C. Taitt15, V. de Pril16, G. de Schaetzen17, S. Suciu17, A. Testori18
  • 1Oncological Surgery, Gustave Roussy Cancer Campus Grand Paris, 94800 - Villejuif/FR
  • 2Department Of Dermatology, IOV-IRCCS, Melanoma Oncology Unit, Padova/IT
  • 3Department Of Dermatology & Skin Cancer, Aix-Marseille University, Hôpital de La Timone APHM, Marseille/FR
  • 4Department Of Dermatology, University of Zürich Hospital, Zurich/CH
  • 5Melanoma And Immunotherapeutics Service, Memorial Sloan-Kettering Cancer Center, New York/US
  • 6Department Of Dermatology, Aarhus University Hospital, DK-8000 - Aarhus C/DK
  • 7Clinical Research, The Angeles Clinic and Research Institute, 90025 - Los Angeles/US
  • 8Dermatology Unit, Gustave Roussy Cancer Campus Grand Paris, 94800 - Villejuif/FR
  • 9Melanoma Cancer Immunotherapy And Innovative Therapy Unit, Istituto Nazionale Tumori Fondazione "G. Pascale", Napoli/IT
  • 10Division Of Hematology/oncology, Oncology Specialists S.C., Park Ridge/US
  • 11Department Of Dermatology, APHP, Dermatology and CIC departments Hôpital Saint Louis, University Paris 7 INSERM U976, Paris/FR
  • 12Department Of Medical Oncology, Istituti Fisioterapici Ospitalieri, Rome/IT
  • 13Department Of Oncology, Cross Cancer Institute, T6G 1Z2 - Edmonton/CA
  • 14Department Of Medicine, H Lee Moffitt Cancer Center (currently at Perlmutter Cancer Center at NYU-Langone Medical Center), Tampa/US
  • 15Worldwide Medical, Bristol-Myers Squibb, Princeton/US
  • 16Worldwide Medical, Bristol-Myers Squibb, Braine-l’Alleud/BE
  • 17Melanoma And Children Leukemia Groups, EORTC Headquarters, Brussels/BE
  • 18Dvisione Nmelaoma E Sarcomi Muscolo-cutanei, European Institute of Oncology, Milan/IT

Abstract

Background

IPI has been an approved treatment for stage III melanoma in the US since 2015, based on a significant improvement in recurrence-free survival (RFS; hazard ratio [HR] 0.75; P = 0.0013) (Eggermont et al, Lancet Oncol, 2015). Here, we report the impact of IPI on overall survival (OS) and distant metastasis-free survival (DMFS).

Methods

In this trial, eligible patients (pts) included those ≥18 yrs of age who underwent complete resection of stage III cutaneous melanoma (excluding lymph node metastasis ≤1 mm or in-transit metastasis alone). 951 pts (20%/44%/36% who had stage IIIA/IIIB/IIIC, 42% ulcerated primary, and 58% macroscopic lymph node involvement) were randomized, stratified by stage and region, 1:1 to IPI 10 mg/kg (n = 475) or PBO (n = 476) q3w for 4 doses, then every 3 mos for up to 3 yrs until completion, disease recurrence, or unacceptable toxicity. The primary endpoint was RFS (updated here). Secondary endpoints included DMFS, OS, and safety.

Results

At 5.3 yrs median follow-up, IPI demonstrated a statistically and clinically significant improvement in OS vs. PBO (HR = 0.72, i.e. 28% risk reduction of death). Similar impact for RFS and DMFS were observed.

RFS DMFS OS
IPI PBO IPI PBO IPI PBO
No. events 264 323 227 279 162 214
5-year rates 40.8% 30.3% 48.3% 38.9% 65.4% 54.4%
Median (mos) 27.6 17.1 48.3 27.5 86.6 NR
HR (CI)† 0.76 (0.64-0.89)* 0.76 (0.64-0.92)** 0.72 (0.58-0.88)***
Log-rank p-value† 0.0008 0.002 0.001

CI: Confidence interval, *95%, **95.8% or ***95.1%; NR: not reached; †stratified by stage Among pts who started IPI (n = 471) or PBO (n = 474), 54.1% (IPI) and 26.2% (PBO) experienced grade 3/4 AEs, consistent with previous reports. The most common grade 3/4 immune-related adverse events (AEs) in the IPI-treated pts were gastrointestinal (16.1%), hepatic (10.8%), and endocrine (7.9%). 251 (53.3%) pts discontinued IPI due to AEs; 5 (1.1%) died due to drug-related AEs.

Conclusions

IPI as adjuvant therapy provided a clinically and statistically significant improvement in OS with a favorable benefit-risk ratio in high-risk stage III melanoma patients. These data reinforce IPI as an important treatment option for these pts.

Clinical trial identification

NCT00636168

Legal entity responsible for the study

Bristol-Myers Squibb

Funding

Bristol-Myers Squibb

Disclosure

A.M.M. Eggermont: Advisory boards for BMS, MSD. V. Chiarion-Sileni: Served in consulting or advisory role for Roche, BMS, GSK, MSD. Participated in speakers' bureau for Roche, BMS, GSK. Travel, accomodations, expenses reimbursed by Roche, GSK, MSD, BMS. J-J. Grob: Served in a consulting or advisory role for BMS, GSK, Novartis, Amgen, Merck Roche. Participated in a speakers' bureau for GSK, Roche, BMS. Conducted research project(s) funded by Roche, BMS. Travel, accomodations, & expenses paid or reimbursed by Roche. R. Dummer: Paid honoraria from Roche, BMS, GSK, MSD, Novartis. Served in consulting or advisory role by Roche, BMS, GSK, MSD, Novartis. Conducted research project(s) funded by Roche, BMS, GSK, MSD, Novartis. J.D. Wolchok: Hon: EMD Serono, Janssen Oncol. Consulting: BMS, Merck, MedImmune, Ziopharm, Polynoma, Polaris, Jounce, GSK. Research funding: BMS, MedImmunce, GSK, Merck. Patent: issued patent for DNA vaccines of cancer in companion animals. Expenses Reimbursed: BMS H. Schmidt: Consultant advisor for Bristol-Myers Squibb, GlaxoSmithKline, Merck, and Roche. He has participated in speakers' bureau for Bristol-Myers Squibb, GlaxoSmithKline, and Roche. O. Hamid: Reports consulting for Amgen, Novartis, Roche, BMS, Merck, Merck Serrano, Pfizer, Genentech. Reports speaker for BMS, Genentech, Novartis, outside the submitted work. C. Robert: Honoraria: BMS, Merck, GSK, Roche, Novartis, Amgen. Consulting or Advisory Role: BMS, Merck, GSK, Roche, Novartis, Amgen. P.A. Ascierto: Honoraria: BMS, Roche-Genentech, GSK. Research Funding: BMS, Roche-Genentech, Ventana. C. Lebbé: Honoraria: BMS, MSD, Roche, Novartis, Amgen. Consulting or Advisory Role: Roche. Research Funding: Roche. Travel, Accomodations, Expenses: BMS, Roche (ASCO, AACR, EADO). M. Smylie: Honoraria: BMS, Roche, GSK, Merck. Consulting or Advisory Role: BMS, Roche, GSK, Merck. Speakers' Bureau: BMS, Roche. J.S. Weber: Stock or Other Ownership: Celldex, Altor, CCAM. Honoraria: BMS, Merck, GSK, Roche, Genentech. Consulting or Advisory Role: BMS, Merck, GSK, Roche, Genentech. Research Funding: BMS, Merck, GSK, Genentech, Roche, Monogenic. C. Taitt: Employee: BMS. Stock or Other Ownership: BMS. V. de Pril: Employee: BMS G. de Schaetzen, S. Suciu: Reports grants from BMS during the conduct of the study. All other authors have declared no conflicts of interest.