Immune checkpoint inhibitors in epidermal growth factor receptor mutant non-small cell lung cancer: Current controversies and future directions

Ross A. Soo, Sun Min Lim, Nicholas L. Syn, Rebecca Teng, Richie Soong, Tony S.K. Mok, Byoung Chul Cho

Research output: Contribution to journalReview articlepeer-review

123 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)12-20
Number of pages9
JournalLung Cancer
Publication statusPublished - 2018 Jan

Bibliographical note

Funding Information:
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 ).

Publisher Copyright:
© 2017 Elsevier B.V.

All Science Journal Classification (ASJC) codes

  • Oncology
  • Pulmonary and Respiratory Medicine
  • Cancer Research


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