AUTHOR=Seegobin Karan , Majeed Umair , Wiest Nathaniel , Manochakian Rami , Lou Yanyan , Zhao Yujie 

TITLE=Immunotherapy in Non-Small Cell Lung Cancer With Actionable Mutations Other Than EGFR

JOURNAL=Frontiers in Oncology

VOLUME=11

YEAR=2021

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2021.750657

DOI=10.3389/fonc.2021.750657

ISSN=2234-943X

ABSTRACT=<p>While first line targeted therapies are the current standard of care treatment for non-small cell lung cancer (NSCLC) with actionable mutations, the cancer cells inevitably acquire resistance to these agents over time. Immune check-point inhibitors (ICIs) have improved the outcomes of metastatic NSCLC, however, its efficacy in those with targetable drivers is largely unknown. In this manuscript, we reviewed the published data on ICI therapies in NSCLC with <italic>ALK</italic>, <italic>ROS1</italic>, <italic>BRAF</italic>, <italic>c-MET</italic>, <italic>RET</italic>, <italic>NTRK</italic>, <italic>KRAS</italic>, and <italic>HER2 (ERBB2)</italic> alterations. We found that the objective response rates (ORRs) associated with ICI treatments in lung cancers harboring the <italic>BRAF</italic> (0–54%), <italic>c-MET</italic> (12–49%), and <italic>KRAS</italic> (18.7-66.7%) alterations were comparable to non-mutant NSCLC, whereas the ORRs in <italic>RET</italic> fusion NSCLC (less than10% in all studies but one) and <italic>ALK</italic> fusion NSCLC (0%) were relatively low. The ORRs reported in small numbers of patients and studies of <italic>ROS1</italic> fusion, <italic>NTRK</italic> fusion, and <italic>HER 2</italic> mutant NSCLC were 0–17%, 50% and 7–23%, respectively, making the efficacy of ICIs in these groups of patients less clear. In most studies, no significant correlation between treatment outcome and PD-L1 expression or tumor mutation burden (TMB) was identified, and how to select patients with NSCLC harboring actionable mutations who will likely benefit from ICI treatment remains unknown.</p>