Osimertinib With Chemo Gains FDA Approval for EGFR-Mutated NSCLC

FDA has approved the targeted therapy osimertinib (Tagrisso, AstraZeneca) with chemotherapy for use in adult patients who were not previously treated for locally advanced or metastatic epidermal growth factor receptor-mutated (EGFRm) non–small cell lung cancer (NSCLC). AstraZeneca announced the approval early today in a statement.

Osimertinib is a third-generation EGFR tyrosine kinase inhibitor (EGFR-TKI) with strong evidence of both progression-free survival (PFS) and, in some studies, overall survival (OS) in patients with EGFR mutations L858R/T790M and exon 19 deletion/T790M.

Of note, a prespecified exploratory analysis from FLAURA2 of patients with brain metastases at baseline showed the combination reduced the risk of central nervous system disease progression or death by 42% compared with osimertinib alone (HR, 0.58; 95% CI, 0.33-1.01). After 2 years, 74% of patients treated with osimertinib and chemotherapy had not experienced CNS disease progression or death, compared with 54% of those receiving osimertinib alone.

The approval was based on results from the phase 3 FLAURA2 trial, published in the New England Journal of Medicine, which found that osimertinib plus chemotherapy extended median PFS by 8.8 months compared with the standard of care. Based on investigator assessment, the combination reduced the risk of disease progression or death by 38% compared with osimertinib alone, which is the first-line standard of care (HR, 0.62; 95% CI, 0.49-0.79; P < .0001). Median PFS for osimertinib with chemotherapy was 25.5 months vs 16.7 months for osimertinib alone. A blinded independent review found the combination produced a 9.5-month improvement over standard of care.

The statement said OS data were immature at the second interim analysis, but at this time “no trend towards a detriment was observed” (HR, 0.75; 95% CI, 0.57-0.97).

“This approval based on the unprecedented data from FLAURA2 brings a critical new treatment option to patients with advanced EGFR-mutated non–small cell lung cancer. Now, with the choice of two highly effective osimertinib-based options, physicians can better tailor treatment to an individual’s needs and help ensure the best possible outcome for each patient,” Pasi A. Jänne, MD, PhD, medical oncologist at Dana-Farber Cancer Institute and principal investigator for the trial, said in the statement from AstraZeneca.

“This important new treatment option can delay disease progression by nearly 9 additional months, establishing a new benchmark with the longest reported progression-free survival benefit in the first-line advanced setting,” added Dave Fredrickson, executive vice president, Oncology Business Unit, AstraZeneca. “This news is especially important for those with a poorer prognosis, including patients whose cancer has spread to the brain and those with L858R mutations.”

Osimertinib after CRT. Along with the new approval, AstraZeneca announced results for the phase 3 LAURA trial, which studied osimertinib in patients with unresectable, stage III EGFRm NSCLC after chemoradiotherapy (CR) compared with placebo after CRT. According to a statement on high-level results from LAURA, Astra Zeneca said that osimertinib produced “statistically significant and highly clinically meaningful improvement in progression-free survival,” and that the therapy was a “key player” in delaying disease progression.

In addition, the statement said that OS data in LAURA were trending favorably for osimertinib but were not mature at this time.

Lung cancer is diagnosed in more than 200,000 people in the United States each year, and 80% to 85% have NSCLC, including 70% with advanced NSCLC. About 15% of those with NSCLC in the United States have an EGFR mutation, according to data from the American Society of Clinical Oncology.