In vivo efficacy of triplet therapy with osimertinib, cetuximab and bevacizumab for lung cancer cells harboring EGFR T790M

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K19454
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Respiratory organ internal medicine
• Research Institution: Okayama University
• Principal Investigator: Ohashi Kadoaki 岡山大学, 大学病院, 講師 (60729193)
• Research Collaborator: Makimoto Go ; Nishii Kazuya
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 非小細胞肺癌 / EGFR変異 / オシメルチニブ / セツキシマブ / ベバシズマブ

Outline of Final Research Achievements

Osimertinib, a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), is the standard treatment for patients with lung cancer harboring EGFR T790M. However, acquired resistance to osimertinib is inevitable, and alternative strategies are needed. We hypothesized that the combination of osimertinib with cetuximab and/or bevacizumab is a more effective treatment than osimertinib monotherapy for lung tumors harboring EGFR T790M. In the xenograft model, the triplet therapy showed no superior effect than doublet therapies (osimertinib plus bevacizumab or osimertinib plus cetuximab) in xenograft model with small tumors. However, the triplet therapy had stronger antitumor effects than osimertinib monotherapy or doublet therapies in xenograft model with larger tumors. The triplet therapy may have an advantage in advanced lung cancer with high tumor volume.

Free Research Field

呼吸器悪性腫瘍

Academic Significance and Societal Importance of the Research Achievements

EGFR遺伝子に変異が起こることで肺癌が発症する。EGFRチロシンキナーゼ阻害薬（TKI）が標準治療であるが、いずれ耐性化して根治は期待できない。本研究では第3世代EGFR-TKIであるオシメルチニブと抗EGFR抗体であるセツキシマブにてがんの原因であるEGFRをより強力に阻害し、さらに血管新生阻害薬ベバシズマブを上乗せする3剤併用療法の効果を基礎的に検討した。この新規3剤併用療法により、単剤治療と比べて強い腫瘍抑制効果が確認できたため、臨床試験で有効性をさらに検討するべき有望な治療法と考える。