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

Nivolumab Plus Erlotinib in Patients With EGFR-Mutant Advanced NSCLC.

Author information

1
Yale Cancer Center, New Haven, Connecticut. Electronic address: scott.gettinger@yale.edu.
2
Memorial Sloan Kettering Cancer Center, New York, New York.
3
University of Washington, Seattle, Washington.
4
Fox Chase Cancer Center, Philadelphia, Pennsylvania.
5
H. Lee Moffitt Cancer Center & Research Institute, Tampa, Florida.
6
The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland.
7
David Geffen School of Medicine at UCLA, Los Angeles, California.
8
UT Southwestern Medical Center, Dallas, Texas.
9
Juravinski Cancer Centre at McMaster University, Hamilton, Ontario, Canada.
10
Princess Margaret Cancer Centre, Toronto, Ontario, Canada.
11
Ottawa Hospital Cancer Centre, Ottawa, Ontario, Canada.
12
Bristol-Myers Squibb, Princeton, New Jersey.

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.

KEYWORDS:

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

PMID:
29802888
DOI:
10.1016/j.jtho.2018.05.015

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