Biomarker analysis of predictors of osimertinib efficacy in non-small cell lung cancer

2022 Fiscal Year Final Research Report

• Project/Area Number: 19K16855
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 50020:Tumor diagnostics and therapeutics-related
• Research Institution: Gunma University
• Principal Investigator: Kasahara Norimitsu 群馬大学, 医学部附属病院, 助教 (10815707)
• Project Period (FY): 2019-04-01 – 2023-03-31
• Keywords: バイオマーカー / 非小細胞肺がん / EGFR遺伝子変異 / オシメルチニブ

Outline of Final Research Achievements

Forty patients with T790M-positive advanced non-small cell lung cancer who received osimertinib after EGFR-TKI treatment progression were enrolled. Plasma samples were collected before osimertinib treatment, 1 month after treatment, and at disease progression. The detection rates of ex19 deletion, L858R, and T790M copy number in plasma samples were significantly lower at 1 month post osimertinib than at pretreatment, and significantly higher at progression than at 1 month, while C797S was significantly higher at progression than at 1 month. Detection of T790M at progression after osimertinib initiation was a significant independent prognostic factor predicting worse prognosis, and the presence of EGFR major mutations at pretreatment and progression was associated with shorter survival after osimertinib initiation.

Free Research Field

腫瘍学

Academic Significance and Societal Importance of the Research Achievements

近年、血中Circulating tumor DNA（ctDNA）の解析により、腫瘍内の不均一性についての分子情報を得られる可能性が指摘されている。しかし上皮成長因子受容体（EGFR）チロシンキナーゼ阻害剤（TKI）治療後のctDNAの効果予測的意義に関するデータは限られている。本研究においてctDNAに基づくEGFR遺伝子変異検査は、EGFR-TKI治療歴のあるT790M陽性NSCLCにおけるオシメルチニブ治療の予後予測に有用であると考えられた。本研究のように採血等を利用した非侵襲的なEGFR-TKIの治療効果の予測を実用化していくことが期待される。