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.

Autor:	Tarhini AA; H. Lee Moffitt Comprehensive Cancer Center, Tampa, FL., Lee SJ; Harvard Medical School, Boston, MA.; Dana-Farber Cancer Institute, Boston, MA., Hodi FS; Dana-Farber Cancer Institute, Boston, MA., Rao UNM; University of Pittsburgh Medical Center, Pittsburgh, PA., Cohen GI; Greater Baltimore Medical Center, Baltimore, MD., Hamid O; Angeles Clinic & Research Institute, Santa Monica, CA., Hutchins LF; University of Arkansas, Little Rock, AR., Sosman JA; Northwestern University Feinberg School of Medicine, Chicago, IL., Kluger HM; Yale University, New Haven, CT., Eroglu Z; H. Lee Moffitt Comprehensive Cancer Center, Tampa, FL., Koon HB; Case Western Reserve University, Cleveland, OH., Lawrence DP; Massachusetts General Hospital, Boston, MA., Kendra KL; Ohio State University, Columbus, OH., Minor DR; Sutter-California Pacific Medical Center, San Francisco, CA., Lee CB; University of North Carolina at Chapel Hill, Chapel Hill, NC., Albertini MR; University of Wisconsin, Madison, WI., Flaherty LE; Wayne State University/Karmanos Cancer Institute, Detroit, MI., Petrella TM; Odette Cancer Center, Toronto, Ontario, Canada., Streicher H; National Cancer Institute, Rockville, MD., Sondak VK; H. Lee Moffitt Comprehensive Cancer Center, Tampa, FL., Kirkwood JM; University of Pittsburgh Medical Center, Pittsburgh, PA.
Jazyk:	angličtina
Zdroj:	Journal of clinical oncology : official journal of the American Society of Clinical Oncology [J Clin Oncol] 2020 Feb 20; Vol. 38 (6), pp. 567-575. Date of Electronic Publication: 2019 Dec 27.
DOI:	10.1200/JCO.19.01381
Abstrakt:	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.
Databáze:	MEDLINE
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