Osimertinib was previously approved as a monotherapy, the first-in-line global standard of care, for non–small cell lung cancer indications.
The FDA has approved osimertinib (Tagrisso; AstraZeneca) in combination with chemotherapy for the treatment of adults with locally advanced or metastatic epidermal growth factor receptor-mutated (EGFRm) non–small cell lung cancer (NSCLC), according to a press release from the company.1
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“This approval based on the unprecedented data from FLAURA2 brings a critical new treatment option to patients with advanced EGFR[m] [NCSLC]. Now, with the choice of 2 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, a medical oncologist at Dana-Farber Cancer Institute, said in the press release.1
Trial Name: A Study of Osimertinib With or Without Chemotherapy as 1st Line Treatment in Patients With Mutated Epidermal Growth Factor Receptor Non-Small Cell Lung Cancer
ClinicalTrial.gov ID: NCT04035486
Sponsor: AstraZeneca
Estimated Completion Date: June 2026
The approval, following priority review, was based on the FLAURA2 (NCT04035486) phase 3 trial, demonstrating the reduced risk of disease progression or death by approximately 38% compared to osimertinib as a monotherapy, the first-in-line global standard of care. The median progression free survival (PFS) as of investigator assessment was 25.5 months and 16.7 months, respectively, equating to an 8.8-month improvement. PFS by blinded independent central review were consistent with these results, demonstrating a 9.5-month improvement at 29.4 months and 19.9 months, respectively. According to the press release, overall survival had not matured at the second interim analysis at 41% of maturity, with no trends towards detriment.1
Furthermore, the prespecified exploratory analysis showed that patients with brain metastases at baseline showed osimertinib with chemotherapy reduced the risk of central nervous system (CNS) disease progression or death by approximately 42% when compared to osimertinib alone, according to the press release. In 2-year follow-up data, approximately 74% of individuals treated with osimertinib and chemotherapy did not experience CNS disease progression or death compared to 54% with osimertinib alone.1
“This important new treatment option can delay disease progression by nearly nine additional months, establishing a new benchmark with the longest reported progression-free survival benefit in the 1st-line advanced setting. This approval reinforces [osimertinib] as the backbone of EGFR[m] lung cancer treatment either as monotherapy or in combination with chemotherapy. 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,” Dave Fredrickson, the executive vice president of Oncology Business Unit at AstraZeneca, said in the press release.1
The safety profile of osimertinib with chemotherapy was generally manageable and consistent for the profiles of the individual medications, according to the press release. Adverse events (AEs) were higher in osimertinib plus chemotherapy arm, but investigators determined that chemotherapy-related AEs. Discontinuation rates were low in both arms for osimertinib at 11% for the plus chemotherapy arm and 6% for the monotherapy arm.1 Furthermore, there were new safety concerns identified, according to another press release.2
The results for the FLAURA2 phase 3 trial were posted in The New England Journal of Medicine.1,3 The trial will continue to assess OS as the secondary endpoint, according to a press release.2
