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Ipilimumab versus placebo after complete resection of stage III melanoma: Initial efficacy and safety results from the EORTC 18071 phase III trial.
Abstracts that were granted an exception in accordance with ASCO's Conflict of Interest Policy are designated with a caret symbol (^).
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.
|No. RFS events||294||234|
|3-Year rates (SE)||34.8% (2.4%)||46.5% (2.5%)|
|HR (95% CI)||0.75 (0.64–0.90)|
|Log-rank||P = 0.0013|
Abstracts by Alexander M. Eggermont:
Multiplex bead-based measurement of humoral immune responses against tumor-associated antigens in stage II melanoma patients: Side study of the EORTC 18961 trial.Meeting: 2016 ASCO Annual Meeting | Abstract No: 3032
- Meeting: 2015 Genitourinary Cancers Symposium | Abstract No: 316
Long-term results of ultrasound (US)-guided fine needle aspiration cytology (FNAC) in conjunction with sentinel node biopsy (SNB) to support step-wise approach in melanoma.Meeting: 2015 ASCO Annual Meeting | Abstract No: 9067
Presentations by Alexander M. Eggermont:
Randomized phase III trial comparing postoperative adjuvant ganglioside GM2-KLH/QS-21 vaccination versus observation in stage II (T3-T4N0M0) melanoma: Final results of study EORTC 18961.Meeting: 2010 ASCO Annual Meeting Abstract No: 8505Session: Melanoma/Skin Cancers (Oral Abstract Session)
Ipilimumab versus placebo after complete resection of stage III melanoma: Initial efficacy and safety results from the EORTC 18071 phase III trial.Meeting: 2014 ASCO Annual Meeting Abstract No: LBA9008Session: Melanoma/Skin Cancers (Oral Abstract Session)
Meeting: 2014 ASCO Annual Meeting
Session: 50 Years of Precision Medicine: Advances in the Field and Prospective and Innovative Randomized Clinical Trials (Education Session)