☆ 4.7 Article

Biomarkers of Osimertinib Response in Patients with Refractory, EGFR-T790M-positive Non-Small Cell Lung Cancer and Central Nervous System Metastases: The APOLLO Study

CLINICAL CANCER RESEARCH (2020)

Journal

CLINICAL CANCER RESEARCH

Volume 26, Issue 23, Pages 6168-6175

Publisher

AMER ASSOC CANCER RESEARCH

DOI: 10.1158/1078-0432.CCR-20-2081

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Funding

AstraZeneca Pharmaceuticals
National Key Research and Development Projects of China [2018YFC1312201]
Key Research and Development Program of Shandong Province [2016CYJS01A03]
Innovation Project of Shandong Academy of Medical Sciences [2019-04]
Academic Promotion Program of Shandong First Medical University [2019ZL002]
AstraZeneca China

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Abstract

Purpose: Dynamic biomarker monitoring may inform pathways for treating EGFR-T790M-positive non-small cell lung cancer (NSCLC) and central nervous system (CNS) metastases with osimertinib. This study aimed to determine the efficacy and safety of osimertinib for real-world patients with EGFR-T790M NSCLC and CNS metastases and to explore potential circulating biomarkers of therapeutic response. Patients and Methods: APOLLO (ClinicalTrials.gov registration: NCT02972333) was a prospective, single-arm, open-label trial which ran from January 2017 to April 2019. Eligible patients had confirmed EGFR-T790M-positive NSCLC, prior treatment with an EGFR-tyrosine kinase inhibitor, and CNS metastases. All enrolled patients received oral osimertinib 80 mg once daily until disease progression or intolerable toxicity. Primary outcome was overall progression-free survival (PFSo) and secondary outcomes included objective response rate (ORR) and adverse events (AE). Exploratory biomarker analysis involved collection of plasma and cerebrospinal fluid (CSF) samples for next-generation sequencing and drug penetration analysis. Results: From January to September 2017, 38 patients were enrolled. After a median follow-up of 8.2 months (range, 0.07-15.6), 23 (60.5%) of 38 patients had disease progression or death. Median PFSo was 8.4 months [95% confidence interval (CI), 5.8-10.9]. Overall ORR was 39.4%. Twelve (31.6%) of 38 patients had >= 1 grade 3-4 AE. Median osimertinib CSF penetration rate was 31.7%. Patients with undetectable plasma EGFR mutations at week 6 had improved PFSo compared with those with detectable mutations (not reached vs. 4.5 months; 95% CI, 0.0-1.1; P < 0.05). Conclusions: Osimertinib had potent activity against EGFRT-790M-positive NSCLC with CNS metastases. Dynamic monitoring of plasma EGFR may suffice for predicting clinical responses, mitigating the need for repeat CSF biopsy.

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Osimertinib versus afatinib in patients with T790M-positive, non-small-cell lung cancer and multiple central nervous system metastases after failure of initial EGFR-TKI treatment

Yang Yang, Qilong Liu, Lei Cao, Wei Sun, Xiaowei Gu, Bin Liu, Na Xiao, Fei Teng, Xiaoli Li, Meiji Chen, Weiguang Yu, Huanyi Lin, Guixing Xu

Summary: In patients with T790M-positive NSCLC and multiple CNS metastases after failure of initial EGFR-TKI treatment, OSI may be associated with significantly improved survival benefit compared with AFA, with a controllable tolerability profile.

BMC PULMONARY MEDICINE (2021)