Biomarkers of osimertinib response in patients with refractory, EGFR-T790M-positive non-small cell lung cancer and central nervous system metastases:the APOLLO study

Lung Cancer

Clin Cancer Res. 2020 Aug 17:clincanres.2081.2020. doi: 10.1158/1078-0432.CCR-20-2081. Online ahead of print.


INTRODUCTION: 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.

METHODS: APOLLO ( registration NCT02972333) was a prospective, single-arm, open-label trial which ran from Jan 2017 to Apr 2019. Eligible patients had confirmed EGFR-T790M-positive NSCLC, prior treatment with an EGFR-tyrosine kinase inhibitor and CNS metastases. 38 patients were enrolled from eight sites and received oral osimertinib 80 mg once daily until disease progression or intolerable toxicity. Primary outcome was overall progression-free survival; secondary outcomes included objective response rate and adverse events. Exploratory biomarker analysis involved collection of plasma and cerebrospinal fluid samples for next-generation sequencing and drug penetration analysis.

RESULTS: After a median follow-up 8.2 months (range, 0.07-15.6), 23 patients (60.5%) had progression or death. Median overall progression-free survival was 8.4 months (95% CI, 5.8-10.9). Overall objective response rate was 39.4%. 12 patients had ≥1 grade 3-4 adverse event (31.6%). Median osimertinib CSF penetration rate was 31.7%. Patients with undetectable plasma EGFR mutations at Week 6 had improved overall progression-free survival compared to 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 EGFR-T790M-positive NSCLC with CNS metastases. Dynamic monitoring of plasma EGFR may suffice for predicting clinical responses, mitigating the need for re-biopsy.