According to the findings of the phase 3 FLAURA2 study, patients with EGFR-mutated advanced NSCLC benefited considerably from the addition of osimertinib to platinum-pemetrexed treatment. Osimertinib is an oral, irreversible third-generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI).
The findings call into question the present standard of care for first-line treatment and point to osimertinib in conjunction with chemotherapy as a viable new therapeutic option. Because of the outcomes of the phase 3 FLAURA study, osimertinib is currently the gold standard therapy for patients with EGFR-mutated, advanced NSCLC.
Despite the fact that osimertinib alone is highly effective, the majority of patients still face the difficulty of disease progression. In the FLAURA2 study, researchers coupled osimertinib with the chemotherapeutic drugs platinum and pemetrexed to examine how well they performed together. Â
The safety run-in phase of the study revealed that the combination had a safety profile commensurate with the individual components, providing the opportunity for more investigation before the trial’s randomized phase commenced. According to the findings of the randomized phase, the combination significantly improved progression-free survival compared to osimertinib alone.
According to the investigator evaluation, the median progression-free survival extension was roughly 8.8 months, and according to the central review, it was 9.5 months. The combination’s higher median duration of response may be what prompts the encouraging statistics revealing a prolonged anticancer effect of osimertinib plus chemotherapy.
This finding is consistent with prior trials that combined chemo with first-generation EGFR-TKIs. Extrapulmonary and central nervous system metastases increased in the FLAURA2 study compared to the FLAURA trial, indicating that the combination may be helpful in treating a broader spectrum of disease presentations. Â
Although it is too early to make solid conclusions regarding overall survival, the findings suggest that combining osimertinib with chemotherapy had no negative impact on patient outcomes. A second examination of progression-free survival provides additional evidence for the combination’s positive effect on subsequent treatment efficacy. Â
Predictive biomarkers for the combination of osimertinib and platinum-pemetrexed may be developed through current exploratory research, such as that based on circulating tumor DNA, which may illuminate the mechanisms behind the therapeutic benefit seen with this treatment.Â
Despite the underrepresentation of some ethnic and cultural groups, particularly Black patients, the FLAURA2 research included a diverse group of people from all over the world. Regardless, increased progression-free survival appears to be a universal benefit for persons of all ages and illness types. Â
When osimertinib was coupled with platinum-pemetrexed, the incidence of grade 3 adverse events increased, and the majority of these were hematologic toxic effects similar to those found with chemotherapy-induced bone marrow suppression. Despite these obstacles, the findings of this trial indicate that the combination is a feasible new treatment option for patients with EGFR-mutated advanced NSCLC. Â
The research had certain limitations, such as recruiting only patients with common EGFR mutations and using an open-label design. Still, the results were persuasive enough to imply that osimertinib with platinum-pemetrexed might be a game changer for first-line therapy of EGFR-mutated advanced NSCLC. These findings highlight the importance of ongoing research in this fast-growing field and provide hope for new therapy options. Â
Journal Reference Â
Planchard, D., Jänne, P. A., Cheng, Y., Yang, J. C.-H., Yanagitani, N., Kim, S.-W., … Kobayashi, K. (2023). New England Journal of Medicine, 389(21), 1935–1948. doi:10.1056/nejmoa2306434Â
