Safety profile of nivolumab administered as 30-min infusion: analysis of data from CheckMate 153
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Nivolumab has been administered using a 60-min infusion time. Reducing this time to 30 min would benefit both patients and infusion facilities. This analysis compared the safety of 30- and 60-min infusions of nivolumab in patients with previously treated advanced non-small cell lung cancer.
CheckMate 153 is an open-label, phase 3b/4, predominantly community-based study ongoing in the United States and Canada. Patients with stage IIIB/IV disease with progression/recurrence after at least one prior systemic therapy received nivolumab 3 mg/kg every 2 weeks over 30 or 60 min for 1 year or until disease progression. The primary outcome overall was to estimate the incidence of grade 3–5 treatment-related select adverse events; a retrospective objective was to estimate the incidence of hypersensitivity/infusion-related reactions (IRRs) with the 30-min infusion. Exploratory pharmacokinetic analyses were performed using a population pharmacokinetics model.
Of 1420 patients enrolled, 369 received only 30-min infusions and 368 received only 60-min infusions. Similar frequencies of hypersensitivity/IRRs were noted in patients receiving 30-min [2% (n = 8)] and 60-min [2% (n = 7)] infusions. Grade 3–4 treatment-related hypersensitivity/IRRs led to treatment discontinuation in < 1% of patients in each group; < 1% of patients in each group received systemic corticosteroids. Hypersensitivity/IRRs were managed by dosing interruptions, with minimal impact on total dose received. Nivolumab pharmacokinetics were predicted to be similar in the two groups.
Nivolumab infused over 30 min had a comparable safety profile to the 60-min infusion, including a low incidence of IRRs.
Keywords30-min infusion Infusion time Nivolumab Non-small cell lung cancer Pharmacokinetics
We thank the patients and families who made this trial possible, the clinical study teams who were involved in this trial, Bristol-Myers Squibb (Princeton, NJ), and ONO Pharmaceutical Co, Ltd (Osaka, Japan). We would also like to thank Jun Shen of Bristol-Myers Squibb for assisting with the simulation of nivolumab pharmacokinetics.
Medical writing and editorial assistance were provided by Mark Palangio and Anne Cooper of StemScientific, funded by Bristol-Myers Squibb. Preliminary results from this analysis were presented at the American Society of Clinical Oncology 2016 Annual Meeting; June 3–7, 2016; Chicago, IL, USA; Poster 3059. This study was funded by Bristol-Myers Squibb. The funder provided the study drug and worked with investigators to design and conduct the study and to collect, manage, analyze, and interpret the data. The funder, in collaboration with the authors, contributed to the preparation, review, and approval of the manuscript and the decision to submit the manuscript for publication.
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Conflict of interest
Dr Waterhouse has participated in speakers’ bureau for Genentech, Eli Lilly, Celgene, and Bristol-Myers Squibb, where he also served in a consulting and/or an advisory role. Dr Horn has served in a consulting and/or an advisory role for Genentech, Merck, Bristol-Myers Squibb, Boehringer Ingelheim, XCovery, and Bayer; she received research funding from a2 Pharmaceutical; and she disclosed a financial relationship with Biodesix. Dr Reynolds has reported stock or ownership interest in Gilead; he has served in a consulting and/or an advisory role for, and received travel, accommodations, expenses, and honoraria from, Eli Lilly, Boehringer Ingelheim, Bristol-Myers Squibb, Genentech, and AstraZeneca; he has participated in a speakers’ bureau for Eli Lilly, Boehringer Ingelheim, Genentech, and AstraZeneca. Dr Spigel has served in a consulting and/or an advisory role for Novartis and Genentech; he has received travel, accommodations, and expenses from Novartis, Genentech, and Pfizer. Dr Chandler has served in a consulting and/or an advisory role for, and received travel, accommodations, and expenses from, Bristol-Myers Squibb, Janssen, and Caris Life Sciences. Dr Mekhail has participated in a speakers’ bureau for, and received research funding and honoraria from, Bristol-Myers Squibb. Dr Mohamed has served in a consulting and/or an advisory role for, and has participated in a speakers’ bureau for, Eli Lilly, Boehringer Ingelheim, Bristol-Myers Squibb, Genentech, and Merck. Dr Creelan has participated in a speakers’ bureau for, and has received travel, accommodations, and expenses from, Bristol-Myers Squibb and AstraZeneca; he has received research funding and honoraria from Boehringer Ingelheim. Dr. Blankstein has no financial relationships to disclose. Dr Nikolinakos has served in a consulting and/or an advisory role for Eli Lilly, Boehringer Ingelheim, and Exelixis; he has participated in a speakers’ bureau for Boehringer Ingelheim. Dr McCleod has no financial relationships to disclose. Mr Li has been employed by and owns stock in Bristol-Myers Squibb Company. Dr Oukessou has been employed by and owns stock in Bristol-Myers Squibb Company. Dr Agrawal has been employed by and owns stock in Bristol-Myers Squibb Company. Dr Aanur has been employed by and owns stock in Bristol-Myers Squibb Company. No others disclosures were reported.
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. This article does not contain any studies with animals performed by any of the authors.
Informed consent was obtained from all individual participants included in the study.
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