SINGAPORE ― For Asian patients with EGFR-mutated non–small cell lung cancer (NSCLC), progression-free survival (PFS) is significantly improved with the third-generation EGFR tyrosine kinase inhibitor (TKI) osimertinib (Tagrisso, AstraZeneca), a subset analysis of phase 3 trial data indicates.
The FLAURA (NCT02296125) trial, which compared osimertinib with current standard-of-care (SOC) therapies in 556 patients from Asia, Europe, and North America, was presented earlier this year at the 2017 congress of the European Society for Medical Oncology (ESMO) and has now been published in the New England Journal of Medicine.
As previously reported by Medscape Medical News, the median PFS was 18.9 months with osimertinib vs 10.2 months with SOC therapies (hazard ratio [HR], 0.46; P < .0001). The overall response rates were 80% and 76%, respectively, and the median duration of response was 17.2 months vs 8.5 months.
At the time, experts questioned whether the patients’ race may have had a bearing on treatment outcomes, especially because EGFR mutations are approximately three times more common among Asian NSCLC patients than Western patients, at 30% to 40% vs 10% to 15%.
Now, a subset analysis of the FLAURA study that specifically investated the Asian participants has confirmed that the improved outcomes with osimertinib vs SOC therapy are also seen in the Asian population. This new subanalysis was presented at the 2017 ESMO meeting held recently in Singapore.
The subanalysis shows that osimertinib was associated with a 46% reduced risk for progression and a more than doubling of the median duration of response in comparison with SOC therapies in the Asian patient population.
Lead researcher Byoung Chul Cho, MD, PhD, Yonsei Cancer Center, Seoul, Korea, said in a release: “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. Osimertinib should be the preferred first-line treatment for EGFR-mutant NSCLC in Asia.”
James C. H. Yang, MD, PhD, chairman, Graduate Institute of Oncology, National Taiwan University College of Medicine, Taipei City, agreed that the findings are “quite compatible” with those seen in the overall FLAURA population.
“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,” Dr Yang commented.
Details of Subanalysis
The subanalysis included 322 adult patients who were enrolled at Asian sites for the FLAURA study. Of those patients, 46 were Chinese, 120 were Japanese, and 156 were from other countries in the region.
None of the patients had previously been treated with EGFR-TKI/systemic anticancer therapy for advanced disease. They were randomly assigned in a 1:1 ratio to receive either osimertinib 80 mg once daily or SOC. Participants were stratified by race and mutation status.
As in the overall FLAURA study, osimertinib was associated with a significantly greater median PFS than SOC, at 16.5 months vs 11.0 months (HR, 0.54; P < .0001).
The overall response rate was 80% among osimertinib patients, compared with 75% in patients receiving SOC therapy, although the median duration of response was more than double with osimertinib, at 17.6 months vs 8.7 months.
Median overall survival was not reached in either treatment arm.
There was a slightly higher rate of grade 3/4 adverse events with osimertinib, at 40% vs 48% for SOC therapy, although the rate of adverse events that led to treatment discontinuation was similar, at 13% vs 15%.
Dr Yang highlighted the similarity in adverse events between the two treatment arms, noting: “We tend to think osimertinib is a well-tolerated drug, so these discontinuation rates were surprisingly high and need further investigation.”
He also pointed out that the HR for PFS was numerically lower in non-Asians than in Asians, saying: “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,” he said.
Dr Yang concluded: “It will also be important to know whether Asian and non-Asian patients in the FLAURA trial with brain metastases had similar outcomes.”
The study was funded by AstraZeneca. Dr Cho has received research funding from Novartis, Bayer, AstraZeneca, MOGAM Institute, and Dong-A ST and has consulted for with Novartis, AstraZeneca, Boehringer-Ingelheim, Roche, BMS, Yuhan, Pfizer, and Eli Lilly. Several coauthors have also reported relationships with pharmaceutical companies, and one coauthor is an employee of AstraZeneca.
N Engl J Med. Published online November 18, 2017. Abstract
For more from Medscape Oncology, follow us on Twitter: @MedscapeOnc
Tidak ada komentar:
Posting Komentar