Osimertinib combined with chemotherapy can improve OS in patients with non-small cell lung cancer EGFRm

When Osimertinib/Tagressa was used in combination with pemetrexed and platinum-based chemotherapy, there was a statistically significant and clinically meaningful improvement in overall survival (OS) compared with Osimertinib alone. The positive results come from the phase 3 FLAURA2 trial (NCT04035486), a randomized, open-label trial evaluating patients with locally advanced or metastatic epidermal growth receptor-mutated (EGFRm) non-small cell lung cancer (NSCLC).

Osimertinib is a third-generation irreversibleEGFR tyrosine kinase inhibitor with proven clinical activity in non-small cell lung cancer, including resistance to central nervous system (CNS) metastasis. It is available as 40 mg and 80 mg once-daily oral tablets and is approved by the U.S. Food and Drug Administration for multiple indications and stages of EGFRm NSCLC, either alone or in combination with other agents.

According to the manufacturer, osimertinib is the only targeted therapy shown to improve outcomes in patients with early-stage disease in the Phase 3 NeoADAURA (NCT04351555) and ADAURA trials (NCT02511106) method, a treatment shown to improve outcomes in patients with locally advanced disease in the Phase 3 LAURA trial (NCT03521154), and in the Phase 3 FLAURA (UNC02296125) and FLAURA2 trials (NCT04035486).

In the FLAURA2 trial, 557 patients from more than 150 health centers in 20 countries were enrolled and randomly assigned to receive osimertinib (80 mg once daily) plus chemotherapy (pemetrexed [500 mg/m2 body surface area] plus cisplatin [75 mg/m2] or carboplatin [drug-guided dose]) or osimertinib monotherapy (80 mg once daily). The trial's primary endpoint was progression-free survival (PFS), with osimertinib showing the longest reported median PFS in this setting, and the secondary endpoint was OS.

The researchers reported that osimertinib combined with pemetrexed and platinum-based chemotherapy resulted in a statistically significant and clinically meaningful improvement in OS compared with osimertinib monotherapy. Furthermore, these findings are consistent with previously reported interim OS results and build on the primary endpoint data.

When treating lung cancer, the aim is to extend survival and improve patient experience, especially in the front line where treatment duration is long and many patients remain active. These positive results support osimertinib, either as monotherapy or in combination with chemotherapy, as the standard of care for patients with first-line advanced EGFRm lung cancer and reinforce the meaningful benefit of combination therapy in the current clinical setting. The observed survival benefit is particularly impressive given that FLAURA2 does not place any restrictions on subsequent treatment options after disease progression.

Reported a favorable trend in the osimertinib plus chemotherapy arm (HR 0.75; 95% CI: 0.57-0.97), with consistent results across prespecified subgroups including sex, race, EGFR mutation type, age at diagnosis, smoking history, exercise capacity status, and central nervous system metastasis status at baseline. In addition, osimertinib plus chemotherapy also showed consistent benefit on the prespecified post-progression endpoint of first subsequent therapy (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 therapy (HR 0.69; 95% CI: 0.53-0.99). At the time of this analysis, the OS data were not considered statistically significant; however, the manufacturer reports that the current findings are considered more meaningful.

These excitingOS results provide extensive evidence to support [osimertinib] as a backbone therapy for EGFRm lung cancer, demonstrating that [osimertinib] plus chemotherapy can significantly extend the survival of [first-line] advanced-stage patients, and in addition, previous trials have shown survival benefits for monotherapy in both early- and late-stage patients. With its strong survival benefit and tolerable safety profile, this combination has the potential to help patients live longer while maintaining post-treatment quality of life.

Reference materials:https://go.drugbank.com/drugs/DB09330