Plasma biomarkers for afatinib monotherapy in EGFR-mutated non-small cell lung cancer: Novel insights from companion genomics analysis of the EXTRA study

Plasma biomarkers for afatinib monotherapy in EGFR-mutated non-small cell lung cancer: Novel insights from companion genomics analysis of the EXTRA study

Objectives: Plasma-based testing with circulating cell-free DNA (cfDNA) is an active area of biomarker exploratory studies in patients with non-small cell lung cancer (NSCLC) harboring EGFR mutations. The Exosome-focused Translational Research for Afatinib study prospectively explored novel plasma b...

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Main Authors: Tomonori Makiguchi, Hisashi Tanaka, Kei Morikawa, Aya Hirata, Hidetoshi Itani, Shigeru Tanzawa, Kageaki Watanabe, Hiroyuki Yasuda, Kazuya Horiuchi, Hideyuki Nakagawa, Yoshitaka Seki, Yoshiro Nakahara, Kentaro Hayashi, Nobumasa Takahashi, Takeo Endo, Akihiro Bessho, Tetsuya Okano, Kiyoshi Takeyama, Akikazu Kawase, Makoto Endo, Toshiya Maekura, Kenji Nemoto, Nagio Takigawa, Kazuma Kishi, Kenzo Soejima, Yusuke Okuma, Akira Togashi, Noriyuki Matsutani, Hiroki Shinchi, Koji Ueda, Nobuhiko Seki
Format: Article
Language:English
Published: Elsevier 2025-01-01
Series:Cancer Treatment and Research Communications
Subjects:
Plasma biomarker
Cell-free DNA
Extracellular vesicle-derived DNA
Non-small cell lung cancer
Afatinib
Online Access:http://www.sciencedirect.com/science/article/pii/S2468294225000887
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Summary:Objectives: Plasma-based testing with circulating cell-free DNA (cfDNA) is an active area of biomarker exploratory studies in patients with non-small cell lung cancer (NSCLC) harboring EGFR mutations. The Exosome-focused Translational Research for Afatinib study prospectively explored novel plasma biomarkers for afatinib monotherapy in patients with NSCLC harboring EGFR mutations using genomics, proteomics, epigenomics, and metabolomics. Herein, we present the results of the genomics part. Materials and Methods: Clinical data of afatinib were matched with next generation sequencing (NGS)-based genomics data of cfDNA (n = 101) and extracellular vesicle DNA (evDNA) (n = 99) from pretreatment plasma samples. Results: The detection sensitivity of cfDNA and evDNA mutations was 86 % (87/101) and 37 % (37/99), respectively. When cfDNA mutations were classified into tissue-matched (any EGFR mutations consistent with those identified in tissue) (n = 28), tissue-unmatched (n = 59), and mutation-undetected (n = 14) groups, cfDNA mutation status was a predictor of progression-free survival (PFS) (p < 0.01) and overall survival (OS) (p < 0.01). EvDNA mutation status was a predictor of OS (p < 0.01) rather than PFS (p = 0.48). When the tissue-unmatched cfDNA group was subclassified into EGFR-related (n = 49) and EGFR-unrelated (n = 10) groups, the EGFR-unrelated group had a median PFS and 3-year OS rate of 31.2 months and 80.0 %, respectively. EGFR-unrelated and mutation-undetected cfDNA groups (n = 24) exhibited a median PFS and 3-year OS rate of >30 months and >80 %, respectively, with afatinib monotherapy. Conclusion: This is the first large-scale prospective study of NGS-based concurrent testing for plasma cfDNA and evDNA mutations. The findings suggest that cfDNA mutation status is a promising plasma biomarker for afatinib monotherapy.
ISSN:2468-2942

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