Major advances with the development of epidermal growth factor receptor tyrosine kinase inhibitors and immune check-point inhibitors have ushered in a new era in lung cancer therapy. Whilst pre-clinical studies suggest EGFR-driven NSCLC inhibit antitumor immunity through the activation of the PD-1/PD-L1 pathway, epidemiology studies suggest EGFR mutant NSCLC are more likely to have decreased PD-L1 expression. The superiority of single agent PD-1/PD-L1 inhibitors over docetaxel in pre-treated EGFR mutant NSCLC appears to be moderated. Several mechanisms for a poor response to immune checkpoint have been proposed including a lower tumor mutation burden, and an uninflamed and immunosuppressive tumor microenvironment. Predictive biomarkers to PD-1/PD-L1 inhibitors sensitivity in patients with EGFR mutations are required. The role of EGFR TKI in combination with an immune checkpoint inhibitor is currently being investigated intensively in multiple clinical trials and outcomes from these trials are immature and the optimal sequence, schedule and dosing remains to be determined. A careful evaluation will be required in view of the increased toxicities reported in some of the early studies of combination therapy.
Bibliographical noteFunding Information:
RAS has received honoraria from AstraZeneca, BMS, Boehringer Ingelheim, Lilly, Merck, Novartis, Pfizer, Roche, and Taiho; and research funding from AstraZeneca. TSKM reports receiving fees for serving on advisory boards from AstraZeneca, Roche/Genentech, Eli Lilly and Company, Merck Serono, ACEA Biosciences, Bristol-Myers Squibb, AVEO-Biodesix, Pfizer, Boehringer Ingelheim, Novartis Pharmaceuticals, GlaxoSmithKline, Clovis Oncology, Amgen, Janssen, BioMarin Pharmaceuticals, SFJ Pharmaceuticals, Merck Sharp & Dohme, Vertex Pharmaceuticals, Oncogenex, and Celgene, consulting fees from geneDecode, lecture fees from AstraZeneca, Roche/Genentech, Eli Lilly and Company, Merck Serono, Bristol-Myers Squibb, Pfizer, Boehringer Ingelheim, Novartis Pharmaceuticals, GlaxoSmithKline, Clovis Oncology, Amgen, Merck Sharp & Dohme, and Prime Oncology, and holding stock in Sanomics. BCC has consulting role for Novartis, AstraZeneca, Boehringer-Ingelheim, Roche, BMS, Yuhan, Pfizer, Eli Lilly and has received research funding from Novartis, Bayer, AstraZeneca, MOGAM Institute and Dong-A ST. RCS has received sponsorship from AstraZeneca, Merck, Biorad, Illumina, Perkin Elmer, and ThermoFisher, and research funding from AstraZeneca, Bayer, Illumina, Kyowa Hakka Kirin, and Roche. He has also become a full-time employee of Innovation Exchange Pte Ltd. The authors SML, NLS, and RT declare no conflicts of interest
RAS is supported by the National Research Foundation Singapore and the Singapore Ministry of Education under its Research Centres of Excellence initiative. SML is supported by the National Research Foundation grant funded by the Korea government (No. 2016R1C1B1013299 ), and a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute, funded by the Ministry of Health & Welfare , Republic of Korea (grant number: HI16C1559 ). BCC is supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science , ICT & Future Planning ( 2016R1A2B3016282 ).
All Science Journal Classification (ASJC) codes
- Pulmonary and Respiratory Medicine
- Cancer Research