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The combination regimen had stronger benefits in patients with locally advanced or metastatic epidermal growth receptor-mutated (EGFRm) non–small cell lung cancer (NSCLC) than osimertinib alone.
Osimertinib (Tagrisso; AstraZeneca), when used in combination with pemetrexed and platinum-based chemotherapy, demonstrated a statistically significant and clinically meaningful improvement in overall survival (OS) when compared with osimertinib alone.1 The positive findings are from the phase 3 FLAURA2 trial (NCT04035486), a randomized, open-label trial assessing patients with locally advanced or metastatic epidermal growth receptor-mutated (EGFRm) non–small cell lung cancer (NSCLC).1,2
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Osimertinib is a third-generation, irreversible EGFR-tyrosine kinase inhibitor with proven clinical activity in NSCLC, including against central nervous system (CNS) metastases. Available in 40-mg and 80-mg once-daily oral tablets, it is FDA approved for multiple indications and stages of EGFRm NSCLC, including on its own or in combination with other agents. According to the manufacturers, osimertinib is the only targeted therapy shown to improve patient outcomes in early-stage disease in the phase 3 NeoADAURA (NCT04351555) and ADAURA (NCT02511106) trials, locally advanced stages in the phase 3 LAURA trial (NCT03521154), and late-stage disease in the phase 3 FLAURA (NCT02296125) and FLAURA2 trials (NCT04035486).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 (FLAURA2) (FLAURA2)
ClinicalTrials.gov ID: NCT04035486
Sponsor: AstraZeneca
Completion Date (Estimated): June 3, 2026
For the FLAURA2 trial, a total of 557 patients from over 150 health centers across 20 countries were enrolled and randomly assigned to receive either osimertinib (80 mg once daily) with chemotherapy (pemetrexed [500 mg/m2 of body-surface area] plus either cisplatin [75 mg/m2] or carboplatin [pharmacologically guided dose]) or to receive osimertinib monotherapy (80 mg once daily). The trial’s primary end point was progression-free survival (PFS)—which osimertinib demonstrating the longest-reported median PFS in this setting—and the secondary end point was OS.1-3
The investigators reported that osimertinib with pemetrexed and platinum-based chemotherapy resulted in a statistically significant and clinically meaningful improvement in OS compared with osimertinib monotherapy. Additionally, these findings are consistent with previously reported interim OS results as well as build on the primary end point data.1,4
“When treating lung cancer, the aim is to both prolong survival and improve the patient experience, especially in [first]-line where treatment duration can be long and many patients remain active. These positive results support osimertinib, either as monotherapy or in combination with chemotherapy, as standard of care for patients with [first]-line advanced EGFRm lung cancer and reinforce the meaningful benefit of the combination in the current clinical setting,” FLAURA2 principal investigator Pasi A. Jänne, MD, PhD, senior vice president for translational medicine and thoracic medical oncologist at Dana-Farber Cancer Institute, said in a news release. “The observed survival benefit is particularly impressive given that FLAURA2 did not impose any restrictions on the choice of subsequent treatment after disease progression.”1
The investigators reported that there was a favorable trend with the osimertinib plus chemotherapy arm (HR 0.75; 95% CI 0.57-0.97), with consistent results across prespecified subgroups, including sex, race, type of EGFR mutation, age at time of diagnosis, smoking history, performance status, and CNS metastases status at baseline. Further, osimertinib with chemotherapy also showed a consistent benefit across prespecified postprogression end points of time to first subsequent treatment (HR 0.73; 95% CI 0.56-0.94), time to progression on second-line therapy (HR 0.70; 95% CI 0.52-0.93), and time to second subsequent treatment (HR 0.69; 95% CI 0.51-0.93). At the time of this analysis, the OS data were not considered statistically significant; however, the current findings are considered more meaningful, the manufacturers reported.1,4
“These exciting OS results add to the extensive evidence supporting [osimertinib] as the backbone therapy in EGFRm lung cancer, demonstrating that [osimertinib] plus chemotherapy can significantly extend survival in the [first]-line advanced setting, in addition to prior trials showing survival benefits as monotherapy in both early stage and advanced disease. With its strong survival benefit and tolerable safety profile, this combination has the potential to help patients live longer while maintaining their quality of life on treatment,” Susan Galbraith, executive vice president of oncology hematology research and development, AstraZeneca, said in the news release.1
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