Almonertinib Combined With Cerebral Radiation Treat Brain Metastases From EGFR Positive NSCLC

Summary

According to literature reports, about 16.3%-19% of newly diagnosed NSCLC patients are associated with brain metastasis, and 30%-50% of NSCLC patients will develop brain metastasis during the whole course of the disease. Patients with EGFR positive-type had a 10-15% higher risk of brain metastasis than patients with EGFR wild-type. mOS in patients with EGFR positive were twice as high as those with EGFR wild-type, despite the presence of brain metastasis. Improving the control rate of intracranial lesions in patients with EGFR positive can not only improve the quality of life, but also may translate into survival benefits and improve OS. Previous studies have shown that in lung cancer patients with EGFR-sensitive mutations, craniocerebral radiotherapy prior to delayed craniocerebral radiotherapy significantly prolonged OS. The first-line treatment of the third generation of EGFR-TKI targeting drug Almonertinib for EGFR-positive NSCLC can eliminate the possible EGFR T790M mutant clones at an early stage and better control the disease progression. Moreover, Almonertinib is easy to pass through the blood-brain barrier, which can not only better control intracranial lesions, but also control, prevent or delay the occurrence of brain metastasis. This study was intended to conduct a randomized controlled study on the safety and efficacy of early craniocerebral radiotherapy combined with Almonertinib in patients with EGFR positive non-small cell lung cancer with brain metastasis. Through the above studies we hope to confirm that early craniocerebral radiotherapy combined with Almonertinib is safe and feasible for patients with EGFR positive newly diagnosed with brain metastasis, and can prolong the intracranial progression-free survival (IPFS), and even extend the progression-free survival (PFS) and overall survival (OS).

Timeline

Start

2021-03-01

Primary completion

2024-03-01

Completion

2024-08-01

Publications

• Background Nagasaka M, Zhu VW, Lim SM, Greco M, Wu F, Ou SI. Beyond Osimertinib: The Development of Third-Generation EGFR Tyrosine Kinase Inhibitors For Advanced EGFR+ NSCLC. J Thorac Oncol. 2021 May;16(5):740-763. doi: 10.1016/j.jtho.2020.11.028. Epub 2020 Dec 15.
• Background Dong RF, Zhu ML, Liu MM, Xu YT, Yuan LL, Bian J, Xia YZ, Kong LY. EGFR mutation mediates resistance to EGFR tyrosine kinase inhibitors in NSCLC: From molecular mechanisms to clinical research. Pharmacol Res. 2021 May;167:105583. doi: 10.1016/j.phrs.2021.105583. Epub 2021 Mar 26.
• Background Wakuda K, Yamaguchi H, Kenmotsu H, Fukuda M, Takeshita M, Suetsugu T, Kirita K, Ebi N, Hataji O, Miura S, Chibana K, Okamoto I, Yoshimura K, Nakagawa K, Yamamoto N, Sugio K. A phase II study of Osimertinib for patients with radiotherapy-naive CNS metastasis of non-small cell lung cancer: treatment rationale and protocol design of the OCEAN study (LOGIK 1603/WJOG 9116L). BMC Cancer. 2020 May 1;20(1):370. doi: 10.1186/s12885-020-06874-6.
• Background Franchino F, Ruda R, Soffietti R. Mechanisms and Therapy for Cancer Metastasis to the Brain. Front Oncol. 2018 May 24;8:161. doi: 10.3389/fonc.2018.00161. eCollection 2018.
• Background Nishino M, Soejima K, Mitsudomi T. Brain metastases in oncogene-driven non-small cell lung cancer. Transl Lung Cancer Res. 2019 Nov;8(Suppl 3):S298-S307. doi: 10.21037/tlcr.2019.05.15.
• Background Nieder C, Norum J, Dalhaug A, Aandahl G, Pawinski A. Radiotherapy versus best supportive care in patients with brain metastases and adverse prognostic factors. Clin Exp Metastasis. 2013 Aug;30(6):723-9. doi: 10.1007/s10585-013-9573-x. Epub 2013 Feb 8.
• Background Andrews DW, Scott CB, Sperduto PW, Flanders AE, Gaspar LE, Schell MC, Werner-Wasik M, Demas W, Ryu J, Bahary JP, Souhami L, Rotman M, Mehta MP, Curran WJ Jr. Whole brain radiation therapy with or without stereotactic radiosurgery boost for patients with one to three brain metastases: phase III results of the RTOG 9508 randomised trial. Lancet. 2004 May 22;363(9422):1665-72. doi: 10.1016/S0140-6736(04)16250-8.
• Background Chang JY, Bezjak A, Mornex F; IASLC Advanced Radiation Technology Committee. Stereotactic ablative radiotherapy for centrally located early stage non-small-cell lung cancer: what we have learned. J Thorac Oncol. 2015 Apr;10(4):577-85. doi: 10.1097/JTO.0000000000000453.
• Background Gomez DR, Blumenschein GR Jr, Lee JJ, Hernandez M, Ye R, Camidge DR, Doebele RC, Skoulidis F, Gaspar LE, Gibbons DL, Karam JA, Kavanagh BD, Tang C, Komaki R, Louie AV, Palma DA, Tsao AS, Sepesi B, William WN, Zhang J, Shi Q, Wang XS, Swisher SG, Heymach JV. Local consolidative therapy versus maintenance therapy or observation for patients with oligometastatic non-small-cell lung cancer without progression after first-line systemic therapy: a multicentre, randomised, controlled, phase 2 study. Lancet Oncol. 2016 Dec;17(12):1672-1682. doi: 10.1016/S1470-2045(16)30532-0. Epub 2016 Oct 24.
• Background Garon EB, Siegfried JM, Stabile LP, Young PA, Marquez-Garban DC, Park DJ, Patel R, Hu EH, Sadeghi S, Parikh RJ, Reckamp KL, Adams B, Elashoff RM, Elashoff D, Grogan T, Wang HJ, Dacic S, Brennan M, Valdes Y, Davenport S, Dubinett SM, Press MF, Slamon DJ, Pietras RJ. Randomized phase II study of fulvestrant and erlotinib compared with erlotinib alone in patients with advanced or metastatic non-small cell lung cancer. Lung Cancer. 2018 Sep;123:91-98. doi: 10.1016/j.lungcan.2018.06.013. Epub 2018 Jun 22.
• Results Yang JC, Camidge DR, Yang CT, Zhou J, Guo R, Chiu CH, Chang GC, Shiah HS, Chen Y, Wang CC, Berz D, Su WC, Yang N, Wang Z, Fang J, Chen J, Nikolinakos P, Lu Y, Pan H, Maniam A, Bazhenova L, Shirai K, Jahanzeb M, Willis M, Masood N, Chowhan N, Hsia TC, Jian H, Lu S. Safety, Efficacy, and Pharmacokinetics of Almonertinib (HS-10296) in Pretreated Patients With EGFR-Mutated Advanced NSCLC: A Multicenter, Open-label, Phase 1 Trial. J Thorac Oncol. 2020 Dec;15(12):1907-1918. doi: 10.1016/j.jtho.2020.09.001. Epub 2020 Sep 9.

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