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SINGAPORE-Osimertinib improves progression-free survival compared to standard first-line therapy in Asian patients with EGFR-mutated non-small cell lung cancer (NSCLC), according to the Asian subset analysis of the FLAURA trial presented at the ESMO Asia 2017 Congress (Abstract LBA6_PR), simultaneously published in The New England Journal of Medicine (2017; doi:10.1056/NEJMoa1713137).

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EGFR mutations occur in 30-40 percent of NSCLC in Asian populations compared to 10-15 percent in Western populations. The phase III FLAURA trial compared osimertinib, a third-generation EGFR-tyrosine kinase inhibitor (TKI), to standard-of-care EGFR-TKIs (erlotinib or gefitinib) as first-line therapy in NSCLC patients with EGFR mutations. A total of 556 patients from Asia, Europe, and North America were randomized 1:1 to treatment with osimertinib or standard of care. Osimertinib improved progression-free survival by 54 percent.


This subset analysis included the 322 Asian patients in the FLAURA trial, of whom 46 were Chinese, 120 were Japanese, and 156 were from other parts of Asia.


The median progression-free survival was 16.5 months with osimertinib compared to 11.0 months for the standard therapy, with a hazard ratio of 0.54 (95% confidence interval, 0.41-0.72; p<0.0001).


The median duration of response was two-fold higher for patients treated with osimertinib (17.6 months) compared to standard-of-care (8.7 months). The overall response rate was 80 percent with osimertinib compared to 75 percent with standard-of-care treatment. Median overall survival was not reached. The incidence of grade 3 or higher toxicities was lower for osimertinib (40%) than the standard treatment (48%).


"As in the overall trial population, osimertinib provided a significant progression-free survival benefit in Asian patients with EGFR-mutated NSCLC. Asian patients had similar toxicities with osimertinib as the overall FLAURA population," explained lead author Professor Byoung Chul Cho, MD, PhD, Yonsei Cancer Center, Seoul, Korea. "Osimertinib should be the preferred first-line treatment for EGFR-mutant NSCLC in Asia."


Thoughts on the Study

Commenting on the findings, James CH Yang, MD, PhD, Chairman, Graduate Institute of Oncology, National Taiwan University College of Medicine, Taipei City, said: "The results of this subset analysis are quite compatible with the findings in the overall population presented at the ESMO 2017 Congress in Madrid, Spain (Ann Oncol 2017; 28(Supp 5). We can therefore conclude that osimertinib can be considered as the standard of care for the first-line treatment of Asian advanced NSCLC patients with EGFR mutations.


"The proportion of patients having adverse events that caused them to stop taking osimertinib was similar in the overall (13%) and Asian (15%) populations," he added. "We tend to think osimertinib is a well-tolerated drug so these discontinuation rates were surprisingly high and need further investigation.


"Although there was no statistical difference between the hazard ratios for progression-free survival, it was numerically lower in non-Asians (0.34) compared to Asians (0.54). There is an ongoing debate as to whether Asian and non-Asian patients with EGFR mutations have distinct responses to EGFR-TKIs. This might be due to variations in clinical practice rather than biology. A meta-analysis of all relevant studies could shed light on this issue. It will also be important to know whether Asian and non-Asian patients in the FLAURA trial with brain metastases had similar outcomes," Yang concluded (Ann Oncol 2017;28(Supp 10).