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Activity of afatinib in patients with NSCLC harboring novel uncommon EGFR mutations with or without co-mutations: a case report

Authors :
Petros Christopoulos
Franziska Herster
Petra Hoffknecht
Markus Falk
Markus Tiemann
Hans-Georg Kopp
Andre Althoff
Anja Stammberger
Eckart Laack
Source :
Frontiers in Oncology, Vol 14 (2024)
Publication Year :
2024
Publisher :
Frontiers Media S.A., 2024.

Abstract

Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) represent first-line standard of care in unresectable EGFR mutation-positive (EGFRm+) non-small cell lung cancer (NSCLC). However, 10–20% of patients with EGFRm+ NSCLC have uncommon EGFR variants, defined as mutations other than L858R substitutions or exon 19 deletions. NSCLC harboring uncommon EGFR mutations may demonstrate lower sensitivity to targeted agents than NSCLC with L858R or exon 19 deletion mutations. Prospective clinical trial data in patients with NSCLC uncommon EGFR mutations are lacking. Afatinib is a second-generation TKI and the only Food and Drug Administration-approved drug for some of the more prevalent uncommon EGFR mutations. We present a series of seven case reports describing clinical outcomes in afatinib-treated patients with NSCLC harboring a diverse range of extremely rare mutations with or without co-mutations affecting other genes. EGFR alterations included compound mutations, P-loop αC-helix compressing mutations, and novel substitution mutations. We also present a case with NSCLC harboring a novel EGFR::CCDC6 gene fusion. Overall, the patients responded well to afatinib, including radiologic partial responses in six patients during treatment. Responses were durable for three patients. The cases presented are in line with a growing body of clinical and preclinical evidence that indicating that NSCLC with various uncommon EGFR mutations, with or without co-mutations, may be sensitive to afatinib.

Details

Language :
English
ISSN :
2234943X
Volume :
14
Database :
Directory of Open Access Journals
Journal :
Frontiers in Oncology
Publication Type :
Academic Journal
Accession number :
edsdoj.9d647cfc3ce49f18e8635c29acf8bc3
Document Type :
article
Full Text :
https://doi.org/10.3389/fonc.2024.1347742