Abstract
Osimertinib is more effective as first-line therapy than other EGFR inhibitors for patients with advanced EGFR-mutated non–small cell lung cancer—notably Asians, who have a higher incidence of the disease compared with Western populations. The conclusion is based on data from a subgroup analysis of the phase III FLAURA trial.
The EGFR inhibitor osimertinib (Tagrisso; AstraZeneca) should become the new standard of care for advanced EGFR-mutated non–small cell lung cancer (NSCLC), say investigators involved in the phase III FLAURA trial. A recent subgroup analysis of the study—which earlier established osimertinib's superiority to first-generation EGFR tyrosine kinase inhibitors—shows that the drug significantly prolonged progression-free survival (PFS) in Asian populations. The findings were presented November 18 during the ESMO Asia 2017 Congress in Lugano, Switzerland.
In the trial, 556 previously untreated patients with advanced EGFR-mutated NSCLC were randomized to receive either osimertinib or standard EGFR inhibitor therapy with erlotinib (Tarceva; Genentech) or gefitinib (Iressa; AstraZeneca). The PFS and median duration of response, as reported in The New England Journal of Medicine, were significantly higher among the patients who received osimertinib compared with those who received the other EGFR inhibitors (18.9 vs.10.2 months and 17.2 vs. 8.5 months, respectively).
The results were comparable in a subset of 322 patients from China, Japan, and other parts of Asia, according to data presented at the ESMO meeting, with PFS and median duration of response significantly higher in the intervention group (16.5 vs. 11.0 months and 17.6 vs. 8.7 months, respectively). Investigators noted that EGFR mutations are more common in Asian than Western populations, occurring in 30% to 40% versus 10% to 15% of NSCLC cases, respectively.
“Osimertinib therapy was also associated with better tolerability, including lower skin and liver toxicity,” says the study's senior investigator, Suresh Ramalingam, MD, professor of hematology and medical oncology at Winship Cancer Institute at Emory University in Atlanta, GA. “Considering that it also demonstrated a superior PFS, duration of response, and favorable survival trend compared to standard therapy, it should be considered a new standard of care.”
The PFS benefit in the FLAURA trial also extended to patients with brain metastases at trial entry—a group that has historically had a worse prognosis than patients without metastases.
“Unlike earlier EGFR inhibitors, osimertinib preferentially inhibits mutant as opposed to wild-type EGFR,” notes Pasi A. Jänne, MD, PhD, professor of medicine at Harvard Medical School and director of the Lowe Center for Thoracic Oncology. “We knew from prior studies that it can penetrate the blood–brain barrier easily and be effective for patients with brain metastases; the FLAURA trial confirms that it should no longer be reserved for second-line treatment.”
Osimertinib has already been approved by the FDA as second-line therapy for patients with metastatic EGFR-mutated T790 mutation–positive NSCLC, and it is currently recommended as first-line treatment for EGFR-mutated NSCLC by the National Comprehensive Cancer Network. Researchers are now turning their attention to identifying the factors that cause acquired resistance to the drug.
“We now know that osimertinib should be the first line of attack for patients who develop advanced EGFR-mutant lung cancer,” says Jänne. “Our biggest knowledge gap now is figuring out what fraction of acquired resistance to osimertinib is mediated by development of new EGFR mutations or other mechanisms, and whether those patients can subsequently be treated with EGFR inhibitors or combination therapies.” –Janet Colwell