Scientific Publications Database

Article Title: Nivolumab Plus Erlotinib in Patients With EGFR-Mutant Advanced NSCLC
Authors: Gettinger, Scott; Hellmann, Matthew D.; Chow, Laura Q. M.; Borghaei, Hossein; Antonia, Scott; Brahmer, Julie R.; Goldman, Jonathan W.; Gerber, David E.; Juergens, Rosalyn A.; Shepherd, Frances A.; Laurie, Scott A.; Young, Tina C.; Li, Xuemei; Geese, William J.; Rizvi, Naiyer
Journal: JOURNAL OF THORACIC ONCOLOGY Volume 13 Issue 9
Date of Publication:2018
Abstract:
Introduction: This phase I study evaluated nivolumab combined with erlotinib in patients with advanced EGFR-mutant NSCLC.Methods: Patients with advanced EGFR-mutant NSCLC who were EGFR tyrosine kinase inhibitor (TKI)-naive or TKI-treated but had not received chemotherapy were treated with nivolumab 3 mg/kg every 2 weeks and erlotinib 150 mg/d until disease progression or unacceptable toxicity. The primary objective was safety and tolerability.Results: Twenty patients with TKI-treated and one with TKI-naive EGFR-mutant NSCLC were treated with nivolumab plus erlotinib. Treatment-related grade 3 toxicities occurred in five patients (liver enzyme elevations, n = 2; diarrhea, n = 2; weight loss, n = 1), with no grade >= 4 toxicities. In the TKI-treated population, the objective response rate was 15% (3 of 20, including one complete response), and the 24-week progression-free survival rate was 48%. Responses lasted 13.8, 17.6, and 38.2 months per investigator records. A fourth patient had a nonconventional immune-related response lasting 12.5 months. Among these four patients, two were never-smokers and one each had 35-and <1-pack-year histories. Post-EGFR TKI pre-trial tumor biopsy specimens from these patients detected EGFR T790M mutations in two patients and MNNG HOS Transforming gene (MET) amplification in a third; two patients each had primary EGFR exon 19 deletions or L858R mutations. The TKI-naive patient, who had compound EGFR mutations (L858R and S768I) and ultimately achieved a complete response, had an ongoing response lasting more than 5 years based on investigator records.Conclusions: Nivolumab plus erlotinib was tolerable, with durable responses in patients with EGFR-mutant, TKI-treated NSCLC. (C) 2018 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.