E3611—A Randomized Phase II Study of Ipilimumab at 3 or 10 mg/kg Alone or in Combination with High-Dose Interferon-α2b in Advanced Melanoma
| Autor: | Mark A. Taylor, John M. Kirkwood, Jerry W Mitchell, Phu Van Truong, Ahmad A. Tarhini, Robert M. Conry, Mark R. Albertini, Xiaoxue Li, Noel Laudi, Arun Nagarajan, Uma N. M. Rao, Sandra J. Lee, Stuart J. Wong |
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| Rok vydání: | 2019 |
| Předmět: |
Adult
Male 0301 basic medicine Cancer Research medicine.medical_specialty Phases of clinical research Ipilimumab Kaplan-Meier Estimate Interferon alpha-2 Gastroenterology Article law.invention Young Adult 03 medical and health sciences 0302 clinical medicine Randomized controlled trial law Internal medicine Statistical significance Antineoplastic Combined Chemotherapy Protocols Humans Medicine Neoplasm Metastasis Adverse effect Melanoma Aged Neoplasm Staging Aged 80 and over business.industry Interferon-alpha Middle Aged Confidence interval Treatment Outcome 030104 developmental biology Oncology 030220 oncology & carcinogenesis Toxicity Female business Tremelimumab medicine.drug |
| Zdroj: | Clinical Cancer Research. 25:524-532 |
| ISSN: | 1557-3265 1078-0432 |
| DOI: | 10.1158/1078-0432.ccr-18-2258 |
| Popis: | Purpose: Interferon-α favors a Th1 shift in immunity, and combining with ipilimumab (ipi) at 3 or 10 mg/kg may downregulate CTLA4-mediated suppressive effects, leading to more durable antitumor immune responses. A study of tremelimumab and high-dose interferon-α (HDI) showed promising efficacy, supporting this hypothesis. Patients and Methods: E3611 followed a 2-by-2 factorial design (A: ipi10+HDI; B: ipi10; C: ipi3+HDI; D: ipi3) to evaluate (i) no HDI versus HDI (across ipilimumab doses) and (ii) ipi3 versus ipi10 (across HDI status). We hypothesized that median progression-free survival (PFS) would improve from 3 to 6 months with HDI versus no HDI and with ipi10 versus ipi3. Results: For eligible and treated patients (N = 81) at a median follow-up time of 29.8 months, median PFS was 4.4 months [95% confidence interval (CI), 2.7–8.2] when ipilimumab was used alone and 7.5 months (95% CI, 5.1–11.0) when HDI was added. Median PFS was 3.8 months (95% CI, 2.6–7.5) with 3 mg/kg ipilimumab and 6.5 months (95% CI, 5.1–13.5) with 10 mg/kg. By study arm, median PFS was 8.0 months (95% CI, 2.8–20.2) in arm A, 6.2 months (95% CI, 2.7–25.7) in B, 5.7 months (95% CI, 1.5–11.1) in C, and 2.8 months (95% CI, 2.6–5.7) in D. The differences in PFS and overall survival (OS) did not reach statistical significance. Adverse events were consistent with the known profiles of ipilimumab and HDI and significantly higher with HDI and ipi10. Conclusions: Although PFS was increased, the differences resulting from adding interferon-α or a higher dose of ipilimumab did not reach statistical significance and do not outweigh the added toxicity risks. |
| Databáze: | OpenAIRE |
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