Abstract |
The checkpoint inhibitor nivolumab is active in patients with metastatic melanoma who have failed ipilimumab. In this phase I/II study, we assessed nivolumab's safety in 92 ipilimumab-refractory patients with unresectable stage III or IV melanoma, including those who experienced grade 3-4 drug-related toxicity to ipilimumab. We report long-term survival, response duration, and biomarkers in these patients after nivolumab treatment (3 mg/kg) every 2 weeks for 24 weeks, then every 12 weeks for up to 2 years, with or without a multipeptide vaccine. The response rate for ipilimumab-refractory patients was 30% (95% CI, 21%-41%). The median duration of response was 14.6 months, median progression-free survival was 5.3 months, and median overall survival was 20.6 months, when patients were followed up for a median of 16 months. One- and 2-year survival rates were 68.4% and 31.2%, respectively. Ipilimumab-naïve and ipilimumab-refractory patients showed no significant difference in survival. The 21 patients with prior grade 3-4 toxicity to ipilimumab that was managed with steroids tolerated nivolumab well, with 62% (95% CI, 38%-82%) having complete or partial responses or stabilized disease at 24 weeks. High numbers of myeloid-derived suppressor cells (MDSC) were associated with poor survival. Thus, survival and long-term safety were excellent in ipilimumab-refractory patients treated with nivolumab. Prior grade 3-4 immune-related adverse effects from ipilimumab were not indicative of nivolumab toxicities, and patients had a high overall rate of remission or stability at 24 weeks. Prospectively evaluating MDSC numbers before treatment could help assess the expected benefit of nivolumab.
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Authors | Jeffrey Weber, Geoffrey Gibney, Ragini Kudchadkar, Bin Yu, Pingyan Cheng, Alberto J Martinez, Jodie Kroeger, Allison Richards, Lori McCormick, Valerie Moberg, Heather Cronin, Xiuhua Zhao, Michael Schell, Yian Ann Chen |
Journal | Cancer immunology research
(Cancer Immunol Res)
Vol. 4
Issue 4
Pg. 345-53
(Apr 2016)
ISSN: 2326-6074 [Electronic] United States |
PMID | 26873574
(Publication Type: Clinical Trial, Phase I, Clinical Trial, Phase II, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
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Copyright | ©2016 American Association for Cancer Research. |
Chemical References |
- Antibodies, Monoclonal
- Antineoplastic Agents
- Biomarkers
- Ipilimumab
- Nivolumab
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Topics |
- Adult
- Aged
- Antibodies, Monoclonal
(administration & dosage, adverse effects, therapeutic use)
- Antineoplastic Agents
(administration & dosage, adverse effects, therapeutic use)
- Biomarkers
- Cohort Studies
- Combined Modality Therapy
- Disease Progression
- Drug Resistance, Neoplasm
- Female
- Humans
- Immunophenotyping
- Ipilimumab
- Kaplan-Meier Estimate
- Male
- Melanoma
(drug therapy, immunology, mortality, pathology)
- Middle Aged
- Myeloid Cells
(immunology, metabolism)
- Neoplasm Metastasis
- Neoplasm Staging
- Nivolumab
- Retreatment
- Treatment Outcome
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