• Takayuki Takahama, Koichi Azuma, Mototsugu Shimokawa, Masayuki Takeda, Hidenobu Ishii, Terufumi Kato, Haruhiro Saito, Haruko Daga, Yuko Tsuboguchi, Isamu Okamoto, Kohei Otsubo, Hiroaki Akamatsu, Shunsuke Teraoka, Toshiaki Takahashi, Akira Ono, Tatsuo Ohira, Toshihide Yokoyama, Kazuko Sakai, Nobuyuki Yamamoto, Kazuto Nishio, and Kazuhiko Nakagawa.
• Department of Medical Oncology, Kindai University Faculty of Medicine, Osaka-Sayama, Japan.
• Cancer. 2020 Jan 1; 126 (9): 1940-1948.

BackgroundLiquid biopsy allows the identification of patients whose tumors harbor specific mutations in a minimally invasive manner. No prospective data have been available for the efficacy of osimertinib in patients with non-small cell lung cancer (NSCLC) who develop resistance to first- or second-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) and who test positive for the TKI resistance-conferring T790M mutation of EGFR by liquid biopsy. Therefore, a phase 2 study was conducted to assess the efficacy and safety of osimertinib in such patients.MethodsEligible patients had advanced or recurrent NSCLC with known TKI-sensitizing mutations of EGFR, had documented disease progression after treatment with at least 1 first- or second-generation EGFR TKI, and were positive for the T790M mutation in plasma according to the Cobas EGFR Mutation Test v2 (Roche Diagnostics) or droplet digital polymerase chain reaction analysis. Patients were treated with osimertinib (80 mg/d) until disease progression. The primary endpoint was the overall response rate (ORR) in patients positive for T790M in plasma by the Cobas assay.ResultsBetween June 2016 and November 2017, 276 patients were screened for their T790M status with a liquid biopsy. Seventy-four patients were positive for T790M in plasma, and 53 of these individuals were enrolled in the study. The ORR for evaluable patients positive for T790M in plasma by the Cobas assay (n = 49) was 55.1% (95% confidence interval [CI], 40.2%-69.3%). The median progression-free survival for all evaluable patients (n = 52) was 8.3 months (95% CI, 6.9-12.6 months).ConclusionsThe results demonstrate the utility of liquid biopsy for the detection of T790M with the Cobas EGFR Mutation Test v2. Plasma genotyping with this assay is informative for treatment selection in clinical practice when tumor sampling is not feasible.© 2020 American Cancer Society.

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