The role of comprehensive analysis with circulating tumor DNA in advanced non‐small cell lung cancer patients considered for osimertinib treatment. (12th May 2021)

• Record Type: Journal Article
• Authors: Sueoka‐Aragane, Naoko; Nakashima, Chiho; Yoshida, Hironori; Matsumoto, Naohisa; Iwanaga, Kentaro; Ebi, Noriyuki; Nishiyama, Akihiro; Yatera, Kazuhiro; Kuyama, Shoichi; Fukuda, Minoru; Ushijima, Sunao; Umeguchi, Hitomi; Harada, Daijiro; Kashiwabara, Kosuke; Suetsugu, Takayuki; Fujimoto, Nobukazu; Tanaka, Fumihiro; Uramoto, Hidetaka; Yoshii, Chiharu; Nakatomi, Katsumi; Koh, Genju; Seki, Nobuhiko; Aoe, Keisuke; Nosaki, Kaname; Inoue, Koji; Takamori, Ayako; Kawaguchi, Atsushi
• Is Part Of: Cancer medicine. Volume 10:Number 12(2021)
• Page Start: 3873
• Page End: 3885
• Publication Date: 2021-05-12
• Subjects: molecular diagnosis -- mutations -- next‐generation sequencing -- non‐small cell lung cancer; 616.994005
• DOI: 10.1002/cam4.3929
• Languages: English
• ISSNs: 2045-7634

Abstract

Abstract: Background: EGFR mutations are good predictive markers of efficacy of EGFR tyrosine kinase inhibitors (EGFR‐TKI), but whether comprehensive genomic analysis beyond EGFR itself with circulating tumor DNA (ctDNA) adds further predictive or prognostic value has not been clarified. Methods: Patients with NSCLC who progressed after treatment with EGFR‐TKI, and with EGFR T790 M detected by an approved companion diagnostic test (cobas ® ), were treated with osimertinib. Plasma samples were collected before and after treatment. Retrospective comprehensive next‐generation sequencing (NGS) of ctDNA was performed with Guardant360 ® . Correlation between relevant mutations in ctDNA prior to treatment and clinical outcomes, as well as mechanisms of acquired resistance, were analyzed. Results: Among 147 patients tested, 57 patients received osimertinib, with an overall response rate (ORR) of 58%. NGS was successful in 54 of 55 available banked plasma samples; EGFR driver mutations were detected in 43 (80%) and T790 M in 32 (59%). The ORR differed significantly depending on the ratio (T790 M allele fraction [AF])/(sum of variant AF) in ctDNA ( p = 0.044). The total number of alterations detected in plasma by NGS was higher in early resistance patients ( p = 0.025). T790 M was lost in 32% of patients (6 out of 19) after acquired resistance to osimertinib. One patient with RB1 deletion and copy number gains of EGFR, PIK3CA, and MYC in addition to T790 M, showed rapid progression due to suspected small cell transformation. Conclusions: NGS of ctDNA could be a promising method for predicting osimertinib efficacy in patients with advanced NSCLC harboring EGFR T790 M. Abstract : A retrospective analysis of comprehensive next‐generation sequencing (NGS) of ctDNA in a multi‐center, prospective observational cohort study conducted to examine the efficacy of liquid biopsy as a predictive marker for third generation treatment with the EGFR tyrosine kinase inhibitor (EGFR‐TKI), osimertinib is reported in this paper. We demonstrated that the number of genomic alterations was significantly higher in non‐responders than in responders to osimertinib, suggesting that plasma NGS could be a better method for predicting osimertinib efficacy in patients with advanced NSCLC.