Osimertinib Plus Chemotherapy Approved in EU as First-Line Therapy for EGFR-Mutated Advanced NSCLC

Osimertinib (Tagrisso) plus pemetrexed and platinum-based chemotherapy has been approved in the European Union (EU) as a first-line treatment for adults with advanced EGFR-mutated non-small cell lung cancer (NSCLC) that has exon 19 deletions or exon 21 (L858R) mutations, according to an announcement from the drug manufacturer, AstraZeneca.

The European Commission’s approval of the combination comes after the positive opinion of the Committee for Medicinal Products for Human Use and is based on results from the phase 3 FLAURA2 trial, which were published in the New England Journal of Medicine.

The trial showed osimertinib plus chemotherapy extended median progression-free survival (PFS) by 8.8 months compared with osimertinib monotherapy, which is the “first-line global standard of care,” according to AstraZeneca.

“Today’s news marks a significant advance for patients with EGFR-mutated lung cancer in Europe, providing a new first-line treatment option with osimertinib now in combination with chemotherapy,” David Planchard, MD, PhD, a thoracic oncologist at Gustave Roussy Institute of Oncology and the principal investigator for the trial, said in a statement. “The FLAURA2 results build on the established efficacy of osimertinib monotherapy, showing a meaningful 9-month improvement in [PFS] and offering physicians the option to tailor treatment to a patient’s specific needs.”

The FLAURA2 trial showed the combination reduced the risk of disease progression or death by 38% compared with osimertinib monotherapy, per investigator assessment (hazard ratio [HR], 0.62; 95% CI, 0.49-0.79; P<.0001). The PFS results from blinded independent central review (BICR) were “consistent with the results by investigator assessment,” showing a median PFS of 29.4 months with the combination, a 9.5-month improvement over the monotherapy (19.9 months; HR, 0.62; 95% CI, 0.48-0.80; nominal P=.0002), according to the announcement.

Among patients with brain metastases at baseline, the combination also reduced the risk of central nervous system (CNS) disease progression or death by 42% compared with monotherapy (HR, 0.58; 95% CI, 0.33-1.01), as assessed by BICR. The 2-year follow-up data showed 74% of patients who received the combination had not experienced CNS disease progression or death, compared with 54% of patients who received the monotherapy.

The overall survival (OS) results “remained immature” at the second interim analysis, there was a “trend towards an OS benefit” with the combination compared to the monotherapy (HR, 0.75; 95% CI, 0.57-0.97), company officials said in the announcement. The safety profile of osimertinib plus chemotherapy “was consistent with the established profiles of the individual medicines,” as adverse event (AE) rates were higher in those receiving the combination and were “driven by well-characterized chemotherapy-related AEs,” according to the announcement. The discontinuation rate due to AEs was 11% for the combination therapy and 6% for the monotherapy.

Osimertinib is approved as monotherapy in more than 110 countries, including the United States, the European Union, China, and Japan. Osimertinib plus chemotherapy is also approved as first-line treatment for locally advanced or metastatic EGFR-mutated NSCLC in some countries, including the United States, China, and Japan.

Source: AstraZeneca