Nivolumab Plus Erlotinib in Patients With EGFR-Mutant Advanced NSCLC

J Thorac Oncol. 2018 Sep;13(9):1363-1372. doi: 10.1016/j.jtho.2018.05.015. Epub 2018 May 23.


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.

Keywords: Combination therapy; EGFR-mutant NSCLC; Erlotinib; Nivolumab; Programmed death 1 axis inhibitor.

Publication types

  • Clinical Trial, Phase I
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Erlotinib Hydrochloride / pharmacology
  • Erlotinib Hydrochloride / therapeutic use*
  • Female
  • Humans
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / pathology
  • Male
  • Middle Aged
  • Nivolumab / pharmacology
  • Nivolumab / therapeutic use*


  • Nivolumab
  • Erlotinib Hydrochloride