Nivolumab plus ipilimumab in patients with advanced melanoma: Updated survival, response, and safety data in a phase I dose-escalation study Journal Article


Authors: Callahan, M. K.; Kluger, H.; Postow, M. A.; Segal, N. H.; Lesokhin, A.; Atkins, M. B.; Kirkwood, J. M.; Krishnan, S.; Bhore, R.; Horak, C.; Wolchok, J. D.; Sznol, M.
Article Title: Nivolumab plus ipilimumab in patients with advanced melanoma: Updated survival, response, and safety data in a phase I dose-escalation study
Abstract: Purpose: The clinical activity observed in a phase I dose-escalation study of concurrent therapy with nivo-lumab (NIVO) and ipilimumab (IPI) in patients with previously treated or untreated advanced melanoma led to subsequent clinical development, including randomized trials. Here, we report longterm follow-up data from study CA209-004, including 3-year overall survival (OS). Patients and Methods: Concurrent cohorts 1, 2, 2a, and 3 received escalating doses of NIVO plus IPI once every 3 weeks for four doses, followed by NIVO once every 3 weeks for four doses, then NIVO plus IPI once every 12 weeks for eight doses. An expansion cohort (cohort 8) received concurrent NIVO 1 mg/kg plus IPI 3 mg/kg once every 3 weeks for four doses, followed by NIVO 3 mg/kg once every 2 weeks, which is the dose and schedule used in phase II and III studies and now approved for patients with unre-sectable or metastatic melanoma. Results: Among all concurrent cohorts (N = 94) at a follow-up of 30.3 to 55.0 months, the 3-year OS rate was 63% and median OS had not been reached. Objective response rate by modified WHO criteria was 42%, and median duration of response was 22.3 months. Incidence of grade 3 and 4 treatment-related adverse events was 59%. The most common grade 3 and 4 treatment-related adverse events were increases in lipase (15%), alanine aminotransferase (12%), and aspartate amino-transferase (11%). One treatment-related death (1.1%) occurred in a patient who had multiorgan failure 70 days after the last dose of NIVO plus IPI. Conclusion: This is the longest follow-up for NIVO plus IPI combination therapy in patients with advanced melanoma. The 3-year OS rate of 63% is the highest observed for this patient population and provides additional evidence for the durable clinical activity of immune checkpoint inhibitors in the treatment of advanced melanoma. © 2017 by American Society of Clinical Oncology.
Keywords: adult; cancer survival; treatment response; aged; survival rate; major clinical study; overall survival; fatigue; advanced cancer; diarrhea; drug safety; drug withdrawal; side effect; treatment duration; conference paper; follow up; ipilimumab; melanoma; liver toxicity; phase 2 clinical trial; nausea; vomiting; abdominal pain; arthralgia; chill; coughing; drug dose escalation; dyspnea; fever; pneumonia; pruritus; rash; alanine aminotransferase; alkaline phosphatase; aspartate aminotransferase; death; xerostomia; colitis; phase 3 clinical trial; inoperable cancer; phase 1 clinical trial; hypothyroidism; flatulence; alopecia; amylase; multiple organ failure; dysgeusia; triacylglycerol lipase; metastatic melanoma; decreased appetite; hypophysitis; vitiligo; nivolumab; human; male; female; priority journal
Journal Title: Journal of Clinical Oncology
Volume: 36
Issue: 4
ISSN: 0732-183X
Publisher: American Society of Clinical Oncology  
Date Published: 2018-02-01
Start Page: 391
End Page: 398
Language: English
DOI: 10.1200/jco.2017.72.2850
PROVIDER: scopus
PUBMED: 29040030
DOI/URL:
Notes: Conference Paper -- Export Date: 1 March 2018 -- Source: Scopus
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MSK Authors
  1. Jedd D Wolchok
    608 Wolchok
  2. Neil Howard Segal
    94 Segal
  3. Michael Andrew Postow
    175 Postow
  4. Alexander Meyer Lesokhin
    106 Lesokhin