Promising osimertinib results presented at ELCC
medwireNews: Two studies presented at this year’s European Lung Cancer Conference (ELCC) in Geneva, Switzerland, focus on the third-generation tyrosine kinase inhibitor (TKI) osimertinib in patients with advanced EGFR-mutated non-small-cell lung cancer (NSCLC).
First-line osimertinib in EGFR-mutated NSCLC
Osimertinib is approved by the US FDA for the treatment of patients harbouring the EGFR T790M resistance mutation who have progressed on prior TKI therapy, while the EMA has granted the agent a conditional marketing authorisation. But in the first of the reports discussed here, the authors evaluate its efficacy in the first-line setting.
Among 60 patients with locally advanced or metastatic disease included in two dose-expansion cohorts of the phase I AURA trial, first-line osimertinib resulted in an objective response rate (ORR) of 77%, which is “among the best reported for first-line therapy of EGFR mutated NSCLC”, lead author Suresh Ramalingam (Winship Cancer Institute of Emory University, Atlanta, Georgia, USA) told the press.
When stratified by dose, the ORR was 67% for the 30 patients who received osimertinib at the 80 mg/day dose and 87% for the 30 given the 160 mg/day dose, while the corresponding median progression-free survival (PFS) times were not reached and 19.3 months. Adverse events leading to dose reductions occurred in 10% of patients in the 80 mg/day group and in 47% of those in the 160 mg/day group.
The drug is to be investigated in the phase III setting going head-to-head with either erlotinib or gefitinib, according to the press release.
Plasma genotyping to identify osimertinib benefit
The second report, also an analysis of the AURA trial, assesses the accuracy of plasma genotyping to identify patients who benefit clinically from osimertinib treatment.
The researchers found that “[o]utcomes were robust” for the 179 previously treated NSCLC patients who had a positive tumour biopsy for the T790M mutation and for the 167 participants with a positive plasma test, with ORRs of 62% and 63%, respectively, and median PFS of 9.7 months in both groups.
However, the outcomes were mixed for T790M-negative patients. Specifically, the 58 patients deemed negative as per tumour biopsy results had a poor ORR and median PFS, at 26% and 3.4 months, respectively. But the 104 patients with a negative plasma result had “unexpectedly favourable” outcomes, with an ORR of 46% and median PFS of 8.2 months.
Researcher Geoffrey Oxnard, from Dana-Farber Cancer Institute in Boston, Massachusetts, USA, told the press that these findings suggest “the resistant mutation might be present in just a subset of the cells, or only in some sites of the tumour.”
“A biopsy may not capture the cancer’s resistance across all sites of disease but a blood test does” he continued, adding that patients with a negative plasma test should undergo a tumour biopsy to clarify their T790M status.
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