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Review
. 2021 Feb 15;13(4):804.
doi: 10.3390/cancers13040804.

Targeted Therapy in Advanced and Metastatic Non-Small Cell Lung Cancer. An Update on Treatment of the Most Important Actionable Oncogenic Driver Alterations

David König  1   2 , Spasenija Savic Prince  2   3 , Sacha I Rothschild  1   2
Affiliations
Review

Targeted Therapy in Advanced and Metastatic Non-Small Cell Lung Cancer. An Update on Treatment of the Most Important Actionable Oncogenic Driver Alterations

David König et al. Cancers (Basel). .

Abstract

Due to groundbreaking developments and continuous progress, the treatment of advanced and metastatic non-small cell lung cancer (NSCLC) has become an exciting, but increasingly challenging task. This applies, in particular, to the subgroup of NSCLC with oncogenic driver alterations. While the treatment of epidermal growth factor receptor (EGFR)-mutated and anaplastic lymphoma kinase (ALK)-rearranged NSCLC with various tyrosine kinase inhibitors (TKIs) is well-established, new targets have been identified in the last few years and new TKIs introduced in clinical practice. Even for KRAS mutations, considered for a long time as an "un-targetable" alteration, promising new drugs are emerging. The detection and in-depth molecular analysis of resistance mechanisms has further fueled the development of new therapeutic strategies. The objective of this review is to give a comprehensive overview on the current landscape of targetable oncogenic alterations in NSCLC.

Keywords: ALK gene rearrangements; BRAF mutations; EGFR exon 20 insertions; EGFR mutation; HER2 alterations; KRAS G12C inhibitors; KRAS mutations; MET alterations; NSCLC; NTRK gene fusions; RET gene rearrangements; ROS1 gene rearrangements; oncogenic alterations; targeted therapy.

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Conflict of interest statement

David König received travel grants from Bristol-Myers Squibb (BMS) and Takeda. Spasenija Savic received personal fees from MSD, AstraZeneca, Boehringer Ingelheim, Roche, Pfizer and Thermo Fisher Scientific, outside the submitted work. Sacha Rothschild received honoraria (paid to institution) from AstraZeneca, BMS, Boehringer-Ingelheim, MSD, Novartis and Roche; received consultancy/advisory fees (paid to institution) from AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Eisai, Eli Lilly, Merck, MSD, Novartis, Pfizer, Roche and Takeda. He received research funding from AbbVie, AstraZeneca, BMS, Boehringer-Ingelheim and Merck. He received renumeration for travel and accommodation expenses from Amgen, AstraZeneca, BMS, Boehringer-Ingelheim, MSD and Takeda. S.R. serves as a member of the Federal Drug Commission of the Federal Office of Public Health and as member of the board of the Swiss Group for Clinical Cancer Research (SAKK).

Figures

Figure 1
Figure 1
Molecular oncogenic driver aberrations and targeted therapies. Graphic overview (A). The size of the circles indicates the frequencies of the oncogenic driver aberration (B). The arrow thickness reflects the magnitude of response (ORR) for every targeted agent and the style of the line (continuous, dashed, dotted) the number of patients included in the corresponding clinical trials (C).
See this image and copyright information in PMC

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