Stage-specific efficacy of osimertinib in treatment-naïve EGFR-mutant non-small cell lung cancer according to baseline genetic alterations in circulating tumor DNA

• Published in: Investigational new drugs 2025-01
• Main Authors: Taniguchi, Yoshihiko, Tamiya, Akihiro, Osuga, Mitsuo, Isa, Shun-Ichi, Nakamura, Keiichi, Mizumori, Yasuyuki, Shinohara, Tsutomu, Yanai, Hidetoshi, Nakatomi, Katsumi, Oki, Masahide, Mori, Masahide, Kuwako, Tomohito, Yamazaki, Koji, Shimada, Masahiro, Ando, Masahiko, Koh, Yasuhiro
• Format: Article
• Language: English
• ISSN: 0167-6997; 1573-0646; 1573-0646
• DOI: 10.1007/s10637-024-01500-9

The impact of clinical stage on the effectiveness of osimertinib for epidermal growth factor receptor (EGFR) mutation-positive non-small cell lung cancer (NSCLC) remains unexamined. We investigated osimertinib therapeutic efficacy variation between stage IVA or lower and stage IVB EGFR mutation-positive lung cancers, focusing on differences in pretreatment co-occurring genetic alterations in circulating tumor DNA. This was a secondary analysis of the ELUCIDATOR study, a multicenter prospective observational study in Japan that assessed the mechanisms underlying resistance to osimertinib as a first-line treatment for advanced NSCLC with EGFR mutations. We compared the progression-free survival (PFS), overall survival (OS), and pretreatment co-occurring genetic alterations detected in plasma between patients with stages IVA (n = 83) and IVB disease (n = 84). Multivariate analysis of PFS and OS revealed that stage IVB was associated with a poor prognosis (hazard ratio [HR]: 2.03, 95% confidence interval [CI]: 1.36-3.04, p