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Review
. 2020 Apr:148:102906.
doi: 10.1016/j.critrevonc.2020.102906. Epub 2020 Feb 11.

Novel drugs targeting EGFR and HER2 exon 20 mutations in metastatic NSCLC

Iosune Baraibar  1 , Laura Mezquita  2 , Ignacio Gil-Bazo  3 , David Planchard  4
Affiliations
Review

Novel drugs targeting EGFR and HER2 exon 20 mutations in metastatic NSCLC

Iosune Baraibar et al. Crit Rev Oncol Hematol. 2020 Apr.

Abstract

Approximately 4% of epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC) present EGFR exon 20 in-frame insertions, accounting for 0.3 %-3.7 % of NSCLC. In addition, 2 %-4 % of patients with NSCLC harbor human epidermal growth factor receptor 2 gene (HER2) mutations, being the 90 % of them exon 20 insertions. These mutations confer intrinsic resistance to available EGFR tyrosine kinase inhibitors (TKIs) and anti-HER2 treatments, as they result in steric hindrance of the drug-binding pocket. Therefore, no targeted therapies have been approved for NSCLC patients with EGFR or HER2 exon 20- activating mutations to date and remain an unmet clinical need. Promising efforts to novel treatment development have been made. Early data provide encouraging activity of novel drugs targeting EGFR and HER2 mutations in metastatic NSCLC. In this review we will summarize all the data reported to date about these driver molecular alterations and potential targeted therapies.

Keywords: EGFR; Exon 20; HER2; Non-small cell lung carcinoma; Targeted therapy.

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Conflict of interest statement

Declaration of Competing Interest (1)Iosune Baraibar: Honoraria: Sanofi. Travel, Accomodations, Expenses: Amgen. (1)Laura Mezquita: Sponsored Research: Bristol-Myers Squibb, Boehringer Ingelheim. Consulting, advisory role: Roche Diagnostics, Takeda. Lectures and educational activities: Bristol-Myers Squibb, Tecnofarma, Roche. Travel, Accommodations, Expenses: Roche. Mentorship program with key opinion leaders: funded by AstraZeneca. Ignacio Gil-Bazo: Consulting, advisory role or lectures: AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Eli Lilly, Guardant Health, Merck Sharp and Dohme, Roche. Honoraria: AstraZeneca, Bristol-Myers Squibb, Merck Sharp and Dohme. Travel, Accommodations, Expenses: AstraZeneca, Bristol-Myers Squibb, Merck Sharp and Dohme, Roche. David Planchard: Consulting, advisory role or lectures: AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Daiichi Sankyo, Eli Lilly, Merck, Novartis, Pfizer, prIME Oncology, Peer CME, Roche. Honoraria: AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Eli Lilly, Merck, Novartis, Pfizer, prIME Oncology, Peer CME, Roche. Clinical trials research: AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Eli Lilly, Merck, Novartis, Pfizer, Roche, Medimmun, Sanofi-Aventis, Taiho Pharma, Novocure, Daiichi Sankyo. Travel, Accommodations, Expenses: AstraZeneca, Roche, Novartis, prIME Oncology, Pfizer.

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