Treatment with osimertinib significantly prolonged progression-free survival compared with platinum therapy plus pemetrexed in patients with T790M-positive advanced non-small cell lung cancer (NSCLC) who had disease progression during first-line EGFR tyrosine kinase inhibitor (TKI) therapy, a study presented at the IASLC 17th World Conference on Lung Cancer and simultaneously published in The New England Journal of Medicine has shown.1
Osimertinib, an EGFR TKI that selectively inhibits both EGFR-TKI sensitizing and T790M resistance mutations in patients with NSCLC, is approved for the treatment of patients with metastatic EGFR T790M mutation-positive NSCLC; however, its efficacy compared with platinum-based therapy plus pemetrexed in this population remains unknown.
To compare the efficacy of each treatment in a head-to-head trial, researchers enrolled 419 patients with T790M-positive advanced NSCLC who experienced disease progression after first-line EGFR TKI therapy. Participants were randomly assigned 2:1 to receive osimertinib orally once daily or pemetrexed plus either carboplatin or cisplatin every 3 weeks for up to 6 cycles; maintenance pemetrexed was permitted.
Results of the international, open-label, phase 3 AURA3 trial (ClinicalTrials.gov Identifier: NCT02151981) showed that treatment with osimertinib significantly reduced the risk of progression or death by 70% compared with pemetrexed plus a platinum agent (hazard ratio [HR], 0.30; 95% CI, 0.23-0.41; P <.001). Median progression-free survival was 10.1 months with osimertinib and 4.4 months with pemetrexed plus platinum therapy.
Researchers also found that patients treated with the EGFR TKI were more than 5 times as likely to achieve an objective response (odds ratio [OR], 5.39; 95% CI, 3.47-8.48; P <.001). Researchers found that 71% (95% CI, 65-76) of patients given osimertinib achieved a response vs 31% (95% CI, 24-40) of those who received pemetrexed plus a platinum agent.
Among the 144 patients with central nervous system metastases, osimertinib treatment was associated with a 68% improvement in progression-free survival compared with pemetrexed and a platinum (HR, 0.32; 95% CI, 0.21-0.49); median progression-free survival was 8.5 months and 4.2 months, respectively.
The study further demonstrated that substantially fewer patients in the osimertinib group experienced grade 3 or worse adverse events (23% vs 47%).
1. Mok TS, Wu YL, Ahn MJ, et al. Osimertinib or platinum–pemetrexed in EGFR T790M–positive lung cancer. N Engl J Med. 2016 Dec 6. doi: 10.1056/NEJMoa1612674. [Epub ahead of print]