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 article

50 Citations (Scopus)

Abstract

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
Volume115
DOIs
Publication statusPublished - 2018 Jan

Fingerprint

docetaxel
Epidermal Growth Factor Receptor
Non-Small Cell Lung Carcinoma
Mutation
Tumor Microenvironment
Immunosuppressive Agents
Tumor Burden
Protein-Tyrosine Kinases
Immunity
Lung Neoplasms
Appointments and Schedules
Epidemiology
Biomarkers
Clinical Trials
Therapeutics
Direction compound
Clinical Studies

All Science Journal Classification (ASJC) codes

  • Oncology
  • Pulmonary and Respiratory Medicine
  • Cancer Research

Cite this

Soo, Ross A. ; Lim, Sun Min ; Syn, Nicholas L. ; Teng, Rebecca ; Soong, Richie ; Mok, Tony S.K. ; Cho, Byoung Chul. / Immune checkpoint inhibitors in epidermal growth factor receptor mutant non-small cell lung cancer : Current controversies and future directions. In: Lung Cancer. 2018 ; Vol. 115. pp. 12-20.
@article{9dfb657870734ea69ecd09dccba65e8d,
title = "Immune checkpoint inhibitors in epidermal growth factor receptor mutant non-small cell lung cancer: Current controversies and future directions",
abstract = "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.",
author = "Soo, {Ross A.} and Lim, {Sun Min} and Syn, {Nicholas L.} and Rebecca Teng and Richie Soong and Mok, {Tony S.K.} and Cho, {Byoung Chul}",
year = "2018",
month = "1",
doi = "10.1016/j.lungcan.2017.11.009",
language = "English",
volume = "115",
pages = "12--20",
journal = "Lung Cancer",
issn = "0169-5002",
publisher = "Elsevier Ireland Ltd",

}

Immune checkpoint inhibitors in epidermal growth factor receptor mutant non-small cell lung cancer : Current controversies and future directions. / Soo, Ross A.; Lim, Sun Min; Syn, Nicholas L.; Teng, Rebecca; Soong, Richie; Mok, Tony S.K.; Cho, Byoung Chul.

In: Lung Cancer, Vol. 115, 01.2018, p. 12-20.

Research output: Contribution to journalReview article

TY - JOUR

T1 - Immune checkpoint inhibitors in epidermal growth factor receptor mutant non-small cell lung cancer

T2 - Current controversies and future directions

AU - Soo, Ross A.

AU - Lim, Sun Min

AU - Syn, Nicholas L.

AU - Teng, Rebecca

AU - Soong, Richie

AU - Mok, Tony S.K.

AU - Cho, Byoung Chul

PY - 2018/1

Y1 - 2018/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85034632852&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85034632852&partnerID=8YFLogxK

U2 - 10.1016/j.lungcan.2017.11.009

DO - 10.1016/j.lungcan.2017.11.009

M3 - Review article

C2 - 29290252

AN - SCOPUS:85034632852

VL - 115

SP - 12

EP - 20

JO - Lung Cancer

JF - Lung Cancer

SN - 0169-5002

ER -