Nivolumab Exposure-Response Analyses of Efficacy and Safety in Previously Treated Squamous or Nonsquamous Non-Small Cell Lung Cancer
| Autor: | Jong-Soon Park, Yan Feng, Brian Lestini, Gaurav Bajaj, Friedrich Graf Finckenstein, Amit Roy, Xiaoning Wang, Shruti Agrawal, Akintunde Bello |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
Oncology
Cancer Research medicine.medical_specialty Lung Neoplasms Population Antineoplastic Agents Kaplan-Meier Estimate 03 medical and health sciences 0302 clinical medicine Internal medicine Carcinoma Non-Small-Cell Lung Antineoplastic Combined Chemotherapy Protocols medicine Carcinoma Humans 030212 general & internal medicine education Adverse effect Lung cancer Survival analysis education.field_of_study Clinical Trials as Topic business.industry Cancer Antibodies Monoclonal medicine.disease Survival Analysis Surgery Clinical trial Nivolumab Treatment Outcome 030220 oncology & carcinogenesis Carcinoma Squamous Cell Female business |
| Zdroj: | Clinical cancer research : an official journal of the American Association for Cancer Research. 23(18) |
| ISSN: | 1557-3265 |
| Popis: | Purpose: Nivolumab is a fully human IgG4 monoclonal antiprogrammed death-1 antibody with demonstrated efficacy, including durable responses and prolonged survival, in patients with previously treated, advanced non–small cell lung cancer (NSCLC). Exposure–response (E–R) analyses for efficacy and safety were conducted to inform the benefit–risk assessment of nivolumab in this patient population. Experimental Design: The analyses used clinical trial data from patients with squamous (n = 293) or nonsquamous (n = 354) NSCLC from four clinical trials who received nivolumab doses of 1 to 10 mg/kg every 2 weeks. E–R efficacy analyses were performed by investigating the relationship between time-averaged nivolumab concentration after the first dose (Cavg1) and the probability of overall survival by histology. E–R safety analyses examined relationships between nivolumab Cavg1 and hazards of adverse events leading to discontinuation or death (AEs-DC/D). Results: Nivolumab exposure was not associated with overall survival [the 95% confidence interval (CI) of effect included 1] in patients with squamous (HR, 0.802; 95% CI, 0.555–1.16) or nonsquamous NSCLC (HR, 0.94; 95% CI, 0.683–1.29). Similarly, nivolumab exposure was not associated with AEs-DC/D in the overall population (HR, 0.917; 95% CI, 0.644–1.31). The risk of AEs-DC/D was similar among patients with squamous or nonsquamous histology. Conclusions: Nivolumab monotherapy demonstrated a wide therapeutic margin, as evidenced by relatively flat E–R relationships over the range of exposures produced by doses of 1 to 10 mg/kg every 2 weeks (Q2W), supporting the use of the initially approved dose of 3 mg/kg Q2W in patients with NSCLC. Clin Cancer Res; 23(18); 5394–405. ©2017 AACR. |
| Databáze: | OpenAIRE |
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