Plasma screening for the T790M mutation of EGFR and phase 2 study of osimertinib efficacy in plasma T790M-positive non-small cell lung cancer: West Japan Oncology Group 8815L/LPS study.

Autor: Takahama T; Department of Medical Oncology, Kindai University Faculty of Medicine, Osaka-Sayama, Japan.; Department of Genome Biology, Kindai University Faculty of Medicine, Osaka-Sayama, Japan., Azuma K; Division of Respirology, Neurology, and Rheumatology, Department of Internal Medicine, Kurume University School of Medicine, Kurume, Japan., Shimokawa M; Department of Cancer Information Research, National Kyushu Cancer Center, Fukuoka, Japan.; Department of Biostatistics, Yamaguchi University Graduate School of Medicine, Ube, Japan., Takeda M; Department of Medical Oncology, Kindai University Faculty of Medicine, Osaka-Sayama, Japan., Ishii H; Division of Respirology, Neurology, and Rheumatology, Department of Internal Medicine, Kurume University School of Medicine, Kurume, Japan., Kato T; Department of Thoracic Oncology, Kanagawa Cancer Center, Yokohama, Japan., Saito H; Department of Thoracic Oncology, Kanagawa Cancer Center, Yokohama, Japan., Daga H; Department of Medical Oncology, Osaka City General Hospital, Osaka, Japan., Tsuboguchi Y; Department of Medical Oncology, Osaka City General Hospital, Osaka, Japan., Okamoto I; Research Institute for Diseases of the Chest, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan., Otsubo K; Research Institute for Diseases of the Chest, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan., Akamatsu H; Internal Medicine III, Wakayama Medical University, Wakayama, Japan., Teraoka S; Internal Medicine III, Wakayama Medical University, Wakayama, Japan., Takahashi T; Division of Thoracic Oncology, Shizuoka Cancer Center, Sunto, Japan., Ono A; Division of Thoracic Oncology, Shizuoka Cancer Center, Sunto, Japan., Ohira T; Department of Surgery, Tokyo Medical University, Shinjuku, Japan., Yokoyama T; Department of Respiratory Medicine, Kurashiki Central Hospital, Kurashiki, Japan., Sakai K; Department of Genome Biology, Kindai University Faculty of Medicine, Osaka-Sayama, Japan., Yamamoto N; Internal Medicine III, Wakayama Medical University, Wakayama, Japan., Nishio K; Department of Genome Biology, Kindai University Faculty of Medicine, Osaka-Sayama, Japan., Nakagawa K; Department of Medical Oncology, Kindai University Faculty of Medicine, Osaka-Sayama, Japan.
Jazyk: angličtina
Zdroj: Cancer [Cancer] 2020 Jan 01; Vol. 126 (9), pp. 1940-1948. Date of Electronic Publication: 2020 Feb 05.
DOI: 10.1002/cncr.32749
Abstrakt: Background: Liquid 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.
Methods: Eligible 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.
Results: Between 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).
Conclusions: The 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.)
Databáze: MEDLINE
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