Ipilimumab versus placebo after complete resection of stage III melanoma: Initial efficacy and safety results from the EORTC 18071 phase III trial.

Melanoma/Skin Cancers
Session Type and Session Title: 
Oral Abstract Session, Melanoma/Skin Cancers
Abstract Number: 
J Clin Oncol 32:5s, 2014 (suppl; abstr LBA9008)
Alexander M. Eggermont, Vanna Chiarion-Sileni, Jean Jacques Grob, Reinhard Dummer, Jedd D. Wolchok, Henrik Schmidt, Omid Hamid, Caroline Robert, Paolo Antonio Ascierto, Jon M. Richards, Celeste Lebbe, Virginia Ferraresi, Michael Smylie, Jeffrey S. Weber, Michele Maio, Cyril Konto, Ravichandra Karra Gurunath, Veerle de Pril, Stefan Suciu, Alessandro Testori; Cancer Institute Gustave Roussy, Villejuif, France; IOV-IRCCS, Melanoma Oncology Unit, Padova, Italy; Hôpital de la Timone, Marseille, France; University of Zürich Hospital, Zürich, Switzerland; Memorial Sloan Kettering Cancer Center, New York, NY; Aarhus University Hospital, Aarhus, Denmark; The Angeles Clinic and Research Institute, Los Angeles, CA; Institut Gustave Roussy, Villejuif, France; Istituto Nazionale Tumori Fondazione “G. Pascale”, Naples, Italy; Oncology Specialists S.C., Park Ridge, IL; Hôpital Saint-Louis, Paris, France; Istituti Fisioterapici Ospitalieri, Rome, Italy; Cross Cancer Institute, Edmonton, AB, Canada; H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL; University Hospital of Siena, Istituto Toscano Tumori, Siena, Italy; Bristol-Myers Squibb, Wallingford, CT; EORTC Headquarters, Brussels, Belgium; Bristol-Myers Squibb, Braine-l'Alleud, Belgium; European Institute of Oncology, Milan, Italy

Abstracts that were granted an exception in accordance with ASCO's Conflict of Interest Policy are designated with a caret symbol (^).

Abstract Disclosures


Background: Ipilimumab (Ipi), a fully human monoclonal antibody that blocks cytotoxic T-lymphocyte antigen-4 to augment antitumor immune responses, is an approved treatment for advanced melanoma. Here, we report the results of a phase III trial designed to evaluate Ipi as an adjuvant therapy for resected stage III melanoma at high risk of recurrence. Methods: In this randomized, double-blind 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). 951 pts were randomized (stratified by stage and region) 1:1 to receive Ipi 10 mg/kg (n=475) or placebo (Pbo, n=476) every 3 wks for 4 doses, then every 3 mos for up to 3 yrs until completion, disease recurrence, or unacceptable toxicity. The primary endpoint was recurrence-free survival (RFS), analyzed on the intent-to-treat population. 512 RFS events (recurrence or death) were needed to provide 90% power to detect an Ipi vs Pbo hazard ratio (HR) of 0.75 (2-sided α=5%). Results: Overall, 20%/44%/36% of pts had stage IIIA/IIIB/IIIC, 42% ulcerated primary, and 58% macroscopic lymph node involvement. At a median follow-up of 2.7 yrs, Ipi significantly improved RFS vs Pbo. RFS benefit was consistent across subgroups (e.g., stage IIIB or IIIC, ulcerated primary). Most common grade 3/4 immune-related adverse events (irAEs) in the Ipi and Pbo arms were gastrointestinal (15.9% vs 0.8%), hepatic (10.6% vs 0.2%), and endocrine (8.5% vs 0%). Most irAEs were managed and resolved using established algorithms. Of 471 pts who started Ipi, 245 (52%) discontinued treatment due to AEs [182 (38.6%) within 12 weeks]; 5 (1.1%) died due to drug-related AEs. Conclusions: In this phase III trial, Ipi as adjuvant therapy provided a clinically and statistically significant improvement in RFS vs Pbo for pts with stage III melanoma at high risk of recurrence. AE profile was generally consistent with that observed in advanced melanoma, although with a higher incidence of endocrinopathies. Clinical trial information: NCT00636168. EudraCT Number: 2007-001974-10.

Pbo Ipi
No. RFS events 294 234
3-Year rates (SE) 34.8% (2.4%) 46.5% (2.5%)
Median (mos) 17.1 26.1
HR (95% CI) 0.75 (0.64–0.90)
Log-rank P = 0.0013