Phase III study of adjuvant ipilimumab (3 or 10 mg/kg) versus high-dose interferon Alfa-2b for resected high-risk melanoma: North American Intergroup E1609

Ahmad A. Tarhini*, Sandra J. Lee, F. Stephen Hodi, Uma N.M. Rao, Gary I. Cohen, Omid Hamid, Laura F. Hutchins, Jeffrey A. Sosman, Harriett M. Kluger, Zeynep Eroglu, Henry B. Koon, Donald P. Lawrence, Kari L. Kendra, David R. Minor, Carrie B. Lee, Mark R. Albertini, Lawrence E. Flaherty, Teresa M. Petrella, Howard Streicher, Vernon K. SondakJohn M. Kirkwood

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

Abstract

PURPOSE Phase III adjuvant trials have reported significant benefits in both relapse-free survival (RFS) and overall survival (OS) for high-dose interferon alfa (HDI) and ipilimumab at 10 mg/kg (ipi10). E1609 evaluated the safety and efficacy of ipilimumab at 3 mg/kg (ipi3) and ipi10 versus HDI. PATIENTS AND METHODS E1609 was a phase III trial in patients with resected cutaneous melanoma (American Joint Committee on Cancer 7th edition stage IIIB, IIIC, M1a, or M1b). It had 2 coprimary end points: OS and RFS. A 2-step hierarchic approach first evaluated ipi3 versus HDI followed by ipi10 versus HDI. RESULTS Between May 2011 and August 2014, 1,670 adult patients were centrally randomly assigned (1:1:1) to ipi3 (n = 523), HDI (n = 636), or ipi10 (n = 511). Treatment-related adverse events grade≥3 occurred in 37% of patients receiving ipi3, 79% receiving HDI, and 58% receiving ipi10, with adverse events leading to treatment discontinuation in 35%, 20%, and 54%, respectively. Comparison of ipi3 versus HDI used an intent-to-treat analysis of concurrently randomly assigned patient cases (n = 1,051) and showed significant OS difference in favor of ipi3 (hazard ratio [HR], 0.78; 95.6% repeated CI, 0.61 to 0.99; P = .044; RFS: HR, 0.85; 99.4% CI, 0.66 to 1.09; P = .065). In the second step, for ipi10 versus HDI (n = 989), trends in favor of ipi10 did not achieve statistical significance. Salvage patterns after melanoma relapse showed significantly higher rates of ipilimumab and ipilimumab/anti-programmed death 1 use in the HDI arm versus ipi3 and ipi10 (P ≤ .001). CONCLUSION Adjuvant therapy with ipi3 benefits survival versus HDI; for the first time to our knowledge in melanoma adjuvant therapy, E1609 has demonstrated a significant improvement in OS against an active control regimen. The currently approved adjuvant ipilimumab dose (ipi10) was more toxic and not superior in efficacy to HDI.

Original languageEnglish (US)
Pages (from-to)567-575
Number of pages9
JournalJournal of Clinical Oncology
Volume38
Issue number6
DOIs
StatePublished - Feb 20 2020

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Fingerprint Dive into the research topics of 'Phase III study of adjuvant ipilimumab (3 or 10 mg/kg) versus high-dose interferon Alfa-2b for resected high-risk melanoma: North American Intergroup E1609'. Together they form a unique fingerprint.

Cite this