| Abstract: |
Purpose The addition of nivolumab (anti–programmed death-1 antibody) to ipilimumab (anti–cytotoxic T-cell lymphocyte–associated 4 antibody) in patients with advanced melanoma improves antitumor response and progression-free survival but with a higher frequency of adverse events (AEs). This cross-melanoma study describes the safety profile of the approved nivolumab plus ipilimumab regimen. Methods This retrospective safety review on data from three trials (phase I, II, and III) included patients with advanced melanoma who received at least one dose of nivolumab 1 mg/kg plus ipilimumab 3 mg/kg every 3 weeks 3 4 and then nivolumab 3 mg/kg every 2 weeks until disease progression or unacceptable toxicity while following established guidelines for AE management. Analyses were of all treatment-related AEs, select (immune-related) AEs, time to onset and resolution, and use of immune-modulating agents and their effects on outcome. Results Among 448 patients, median duration of follow-up was 13.2 months. Treatment-related grade 3/4 AEs occurred in 55.5% of patients; 35.7% had treatment-related AEs that led to discontinuation. The most frequent treatment-related select AEs of any grade were skin (64.3%) and GI (46.7%) and of grade 3/4, hepatic (17.0%) and GI (16.3%); 30.1% developed a grade 2 to 4 select AE in more than one organ category. Median time to onset of grade 3/4 treatment-related select AEs ranged from 3.1 (skin) to 16.3 (renal) weeks, and with the exclusion of endocrine AEs, median time to resolution from onset ranged from 1.9 (renal) to 4.5 (pulmonary) weeks, with resolution rates between 79% and 100% while using immune-modulating agents. Four (, 1%) on-study deaths were attributed to therapy. Conclusion Frequency of grade 3/4 treatment-related AEs was higher with nivolumab plus ipilimumab and occurred earlier than historical experience with either agent alone, but resolution rates were similar. Copyright © 2017 by American Society of Clinical Oncology. |
| Keywords: |
adult; aged; disease-free survival; middle aged; survival analysis; retrospective studies; major clinical study; fatigue; mortality; advanced cancer; cancer combination chemotherapy; cancer growth; diarrhea; dose response; drug efficacy; drug safety; drug withdrawal; treatment duration; disease free survival; cancer staging; outcome assessment; follow up; neoplasm staging; cancer grading; ipilimumab; melanoma; progression free survival; liver toxicity; phase 2 clinical trial; skin neoplasms; nausea; vomiting; drug administration schedule; randomized controlled trials as topic; pathology; dose-response relationship, drug; retrospective study; monoclonal antibody; arthralgia; drug dose escalation; fever; pneumonia; pruritus; rash; maculopapular rash; skin tumor; antibodies, monoclonal; disease severity; drug therapy, combination; clinical trials, phase iii as topic; patient safety; colitis; open study; neoplasm invasiveness; headache; phase 3 clinical trial; maximum tolerated dose; phase 1 clinical trial; hyperthyroidism; hypothyroidism; drug administration; clinical trials, phase i as topic; clinical trials, phase ii as topic; adverse drug reaction; metastatic melanoma; randomized controlled trial (topic); phase 2 clinical trial (topic); decreased appetite; phase 3 clinical trial (topic); phase 1 clinical trial (topic); hypophysitis; vitiligo; parasitology; tumor invasion; combination drug therapy; nivolumab; humans; prognosis; human; male; female; priority journal; article; evaluation study; untreated unresectable melanoma
|
