Nivolumab Plus Erlotinib in Patients With EGFR-Mutant Advanced NSCLC

Scott Gettinger, Matthew D. Hellmann, Laura Q.M. Chow, Hossein Borghaei, Scott Antonia, Julie R. Brahmer, Jonathan W. Goldman, David E. Gerber, Rosalyn A. Juergens, Frances A. Shepherd, Scott A. Laurie, Tina C. Young, Xuemei Li, William J. Geese, Naiyer Rizvi

Research output: Contribution to journalArticlepeer-review

133 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)1363-1372
Number of pages10
JournalJournal of Thoracic Oncology
Issue number9
StatePublished - Sep 2018


  • Combination therapy
  • EGFR-mutant NSCLC
  • Erlotinib
  • Nivolumab
  • Programmed death 1 axis inhibitor

ASJC Scopus subject areas

  • Oncology
  • Pulmonary and Respiratory Medicine


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