TY - JOUR
T1 - Immunotherapy in Non-Small Cell Lung Cancer With Actionable Mutations Other Than EGFR
AU - Seegobin, Karan
AU - Majeed, Umair
AU - Wiest, Nathaniel
AU - Manochakian, Rami
AU - Lou, Yanyan
AU - Zhao, Yujie
N1 - Publisher Copyright:
Copyright © 2021 Seegobin, Majeed, Wiest, Manochakian, Lou and Zhao.
PY - 2021/12/1
Y1 - 2021/12/1
N2 - 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 ALK, ROS1, BRAF, c-MET, RET, NTRK, KRAS, and HER2 (ERBB2) alterations. We found that the objective response rates (ORRs) associated with ICI treatments in lung cancers harboring the BRAF (0–54%), c-MET (12–49%), and KRAS (18.7-66.7%) alterations were comparable to non-mutant NSCLC, whereas the ORRs in RET fusion NSCLC (less than10% in all studies but one) and ALK fusion NSCLC (0%) were relatively low. The ORRs reported in small numbers of patients and studies of ROS1 fusion, NTRK fusion, and HER 2 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.
AB - 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 ALK, ROS1, BRAF, c-MET, RET, NTRK, KRAS, and HER2 (ERBB2) alterations. We found that the objective response rates (ORRs) associated with ICI treatments in lung cancers harboring the BRAF (0–54%), c-MET (12–49%), and KRAS (18.7-66.7%) alterations were comparable to non-mutant NSCLC, whereas the ORRs in RET fusion NSCLC (less than10% in all studies but one) and ALK fusion NSCLC (0%) were relatively low. The ORRs reported in small numbers of patients and studies of ROS1 fusion, NTRK fusion, and HER 2 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.
KW - ALK
KW - BRAF
KW - NTRK
KW - RET
KW - ROS-1
KW - c-MET
KW - immunotherapy
KW - targeted mutations
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U2 - 10.3389/fonc.2021.750657
DO - 10.3389/fonc.2021.750657
M3 - Review article
AN - SCOPUS:85121337554
SN - 2234-943X
VL - 11
JO - Frontiers in Oncology
JF - Frontiers in Oncology
M1 - 750657
ER -