TY - JOUR
T1 - Nivolumab Plus Erlotinib in Patients With EGFR-Mutant Advanced NSCLC
AU - Gettinger, Scott
AU - Hellmann, Matthew D.
AU - Chow, Laura Q.M.
AU - Borghaei, Hossein
AU - Antonia, Scott
AU - Brahmer, Julie R.
AU - Goldman, Jonathan W.
AU - Gerber, David E.
AU - Juergens, Rosalyn A.
AU - Shepherd, Frances A.
AU - Laurie, Scott A.
AU - Young, Tina C.
AU - Li, Xuemei
AU - Geese, William J.
AU - Rizvi, Naiyer
N1 - Copyright © 2018 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.
PY - 2018/9
Y1 - 2018/9
N2 - 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.
AB - 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.
KW - Adult
KW - Aged
KW - Aged, 80 and over
KW - Carcinoma, Non-Small-Cell Lung/drug therapy
KW - Erlotinib Hydrochloride/pharmacology
KW - Female
KW - Humans
KW - Lung Neoplasms/drug therapy
KW - Male
KW - Middle Aged
KW - Nivolumab/pharmacology
UR - http://www.scopus.com/inward/record.url?scp=85050070447&partnerID=8YFLogxK
UR - https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=purepublist2023&SrcAuth=WosAPI&KeyUT=WOS:000444520200027&DestLinkType=FullRecord&DestApp=WOS
U2 - 10.1016/j.jtho.2018.05.015
DO - 10.1016/j.jtho.2018.05.015
M3 - Article
C2 - 29802888
SN - 1556-0864
VL - 13
SP - 1363
EP - 1372
JO - Journal of Thoracic Oncology
JF - Journal of Thoracic Oncology
IS - 9
ER -