ONCAlert | 2017 San Antonio Breast Cancer Symposium

More Evidence of Osimertinib's Activity Against Brain Lesions

Published Online:5:17 PM, Thu September 21, 2017

Caicun Zhou, MD, PhD
The third-generation EGFR inhibitor osimertinib (Tagrisso) had substantial clinical activity against brain metastases in Asia-Pacific patients with advanced non–small cell lung cancer (NSCLC) harboring the T790M resistance mutation, an updated analysis of a randomized trial showed.1

The objective response rate (ORR) for all 59 patients with central nervous system (CNS) lesions was 40%, increasing to 70% for the subset of patients evaluable for CNS response. The disease control rate (DCR) with osimertinib was 85% for all patients and 91% for the CNS-evaluable group, as reported at the 2017 ESMO Annual Congress in Madrid, Spain.

“These data are consistent with previous reports of CNS response to osimertinib in patients with T790M-positive advanced NSCLC in global studies and demonstrated clinically meaningful efficacy in Asian-Pacific patients with CNS metastases,” Caicun Zhou, MD, PhD, director of the Department of Oncology at Shanghai Pulmonary Hospital, and colleagues concluded in a poster presentation.

About 40% of patients with EGFR-positive NSCLC develop CNS metastases, which confer a poor prognosis. The median progression-free survival (PFS) for patients with brain lesions ranges between 3 and 6 months with conventional therapy.
Osimertinib is selective for both EGFR tyrosine kinase-sensitizing mutations and the T790M resistance mutation. Data from 2 prior phase II trials of patients with T790M-positive NSCLC that progressed on an EGFR tyrosine kinase inhibitor demonstrated an ORR of 54% for CNS lesions and a DCR (responses plus stable disease) of 92%.2

To assess the consistency of osimertinib CNS activity, Zhou and colleagues evaluated outcomes in the phase II AURA17 trial, an open-label, single-arm study that investigated the safety and efficacy of osimertinib in Asia-Pacific patients with T790M-positive NSCLC that had progression on prior EGFR TKI therapy.1 The trial design included a prespecified subgroup analysis of patients with CNS metastases that were identified by blinded independent committee review (BICR).

Key endpoints for the subgroup analysis included CNS ORR, CNS duration of response, and CNS PFS. The analysis included all patients with at least 1 measurable or nonmeasurable CNS lesion identified at baseline by BICR and a separate evaluation limited to patients evaluable for response (1 or more measurable CNS lesions identified at baseline).

The complete AURA17 dataset comprised 171 patients with T790M-positive NSCLC, 87 of whom had baseline brain scans. The scans identified 1 or more measurable/nonmeasurable CNS lesion in 59 of the 87 patients. The overall analysis of CNS activity included all 59 patients with CNS metastases, and the assessment of evaluable patients was limited to 23 patients with at least 1 measurable CNS lesion at baseline.

The analysis of all patients with CNS lesions showed that osimertinib led to complete responses in 10 patients, partial responses in 15, and stable disease for at least 6 weeks in 25. Two patients had progressive disease, and the remaining 6 were not evaluable. The absolute numbers translated into an ORR of 42% and DCR of 85%.

Among the 23 patients with measurable CNS lesions, treatment with osimertinib led to 1 complete response, 15 partial responses, and stable disease in 5 patients. Only 1 patient had progressive disease, and 1 proved not to be evaluable for response. The ORR was 70% and DCR was 91%.

The median duration of response had yet to be reached in the total patient population with CNS lesions, although the lower limit of 95% confidence intervals was 9.2 months. The median response duration for patients with measurable lesions at baseline was 11 months.

The median CNS PFS had yet to be reached after a median follow-up duration of 7.1 months for all 59 patients with CNS lesions and 8.2 months for the 23-patient subgroup with measurable lesions. The estimated 12-month PFS was 70% (95% CI, 53%-82%) for all the patients with CNS lesions at baseline and 61% (95% CI, 31%-81%) for the subgroup with measurable lesions.

Systemic response to osimertinib was 58% for all patients with CNS lesions at baseline and 61% in the patients with measurable lesions. Biological agreement for CNS and systemic response/nonresponse in the overall and measurable-lesion groups was 58% and 65%, respectively.
  1. Zhou C, Wang M, Cheng Y, et al. Osimertinib in Asia-Pacific patients (pts) with EGFR T790M-positive advanced NSCLC: Updated Phase II study results including progression-free survival (PFS). Poster presented at: 2017 ESMO Annual Congress; September 8-12, 2017; Madrid, Spain. Abstract 1354P.
  2. Goss G, Tsai C, Shepherd F, et al. CNS response to osimertinib in patients with T790M-positive advanced NSCLC: pooled data from two phase II trials. Presented at: 2016 World Conference on Lung Cancer; December 4-7, 2016; Vienna, Austria. Abstract MA16.11.

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