Combination of Osimertinib and Aspirin to Treat EGFR Mutation NSCLC Patients

Summary

The third generation epidermal growth factor receptor-tyrosine Kinase Inhibitor（EGFR-TKI） osimertinib has obvious curative effect for EGFR sensitive mutation and T790M mutation(PMID 27959700), but acquired drug resistance will occur. Previous studies show that apoptosis escape can lead to EGFR-TKI resistance.Osimertinib resistant cells show abnormal activation of PI3K/AKT/BIM activation(PMID 28765329). The classical drug aspirin can effectively decrease AKT phosphorylation and activate of BIM(PMID 28881293).So Investigators speculate that aspirin may decrease the PI3K/AKT/BIM signaling pathways, then promote osimertinib resistant cells apoptosis. The current study aims to evaluate the combination of aspirin and osimertinib in patients with EGFR/T790M mutations.

Timeline

Start

2019-01-01

Primary completion

2023-06-01

Completion

2024-06-01

Publications

• Results Mok TS, Wu Y-L, Ahn M-J, Garassino MC, Kim HR, Ramalingam SS, Shepherd FA, He Y, Akamatsu H, Theelen WS, Lee CK, Sebastian M, Templeton A, Mann H, Marotti M, Ghiorghiu S, Papadimitrakopoulou VA; AURA3 Investigators. Osimertinib or Platinum-Pemetrexed in EGFR T790M-Positive Lung Cancer. N Engl J Med. 2017 Feb 16;376(7):629-640. doi: 10.1056/NEJMoa1612674. Epub 2016 Dec 6.
• Results Shi P, Oh YT, Deng L, Zhang G, Qian G, Zhang S, Ren H, Wu G, Legendre B Jr, Anderson E, Ramalingam SS, Owonikoko TK, Chen M, Sun SY. Overcoming Acquired Resistance to AZD9291, A Third-Generation EGFR Inhibitor, through Modulation of MEK/ERK-Dependent Bim and Mcl-1 Degradation. Clin Cancer Res. 2017 Nov 1;23(21):6567-6579. doi: 10.1158/1078-0432.CCR-17-1574. Epub 2017 Aug 1.
• Results Ma J, Cai Z, Wei H, Liu X, Zhao Q, Zhang T. The anti-tumor effect of aspirin: What we know and what we expect. Biomed Pharmacother. 2017 Nov;95:656-661. doi: 10.1016/j.biopha.2017.08.085. Epub 2017 Sep 4.
• Results Li L, Han R, Xiao H, Lin C, Wang Y, Liu H, Li K, Chen H, Sun F, Yang Z, Jiang J, He Y. Metformin sensitizes EGFR-TKI-resistant human lung cancer cells in vitro and in vivo through inhibition of IL-6 signaling and EMT reversal. Clin Cancer Res. 2014 May 15;20(10):2714-26. doi: 10.1158/1078-0432.CCR-13-2613. Epub 2014 Mar 18.
• Results Li S, Dai W, Mo W, Li J, Feng J, Wu L, Liu T, Yu Q, Xu S, Wang W, Lu X, Zhang Q, Chen K, Xia Y, Lu J, Zhou Y, Fan X, Xu L, Guo C. By inhibiting PFKFB3, aspirin overcomes sorafenib resistance in hepatocellular carcinoma. Int J Cancer. 2017 Dec 15;141(12):2571-2584. doi: 10.1002/ijc.31022. Epub 2017 Sep 14.

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