The study met its primary endpoint of progression-free survival, and overall survival is continuing to be evaluated.
Osimertinib (Tagrisso; AstraZeneca) with chemotherapy significantly reduced risk of disease progression by more than a third in patients with locally advanced (stage 3B/C) or stage 4 metastatic epidermal growth factor receptor-mutated (EGFRm) non-small cell lung cancer (NSCLC) compared to osimertinib alone, according to results from the FLAURA2 study (NCT04035486) published in a recent press release. FLAURA2 is a randomized, open-label, multi-center, and global phase 3 trial evaluating osimertinib and chemotherapy on progression-free survival for patients with locally advanced or metastatic EGFRm NSCLC. Investigators shared results from FLAURA2 at the 2023 World Conference on Lung Cancer.
Osimertinib with chemotherapy also showed clinically meaningful improvement in the study’s primary endpoint, progression-free survival (PFS), across all prespecified subgroups: sex, race, type of EGFR mutation, age at diagnosis, smoking history, and baseline central nervous system (CNS) metastases status.
“Patients received nearly 9 additional months before their EGFRm NSCLC progressed as a result of the addition of chemotherapy to standard-of-care osimertinib, building on the strong efficacy we have already seen with osimertinib monotherapy,” said principal study investigator Pasi A. Jänne, MD, PhD, medical oncologist at Dana-Farber Cancer Institute, in the press release.
Osimertinib plus chemotherapy reduced risk of disease progression by 38% compared to osimertinib alone (hazard ratio [HR] of 0.62; 95% confidence interval [CI] 0.49-0.79; p<0.0001). Osimertinib/chemotherapy extended average PFS 8.8 months compared to osimertinib alone, according to investigator assessment, but blinded independent central review (BICR) shows the treatment combination extended median PFS by 9.5 months (HR of 0.62; 95% CI 0.48-0.80; p=0.0002).
“The compelling FLAURA2 results add to the extensive evidence supporting osimertinib as the backbone therapy in EGFRm NSCLC and establish a new benchmark for PFS in this setting,” said Susan Galbraith, executive vice president, Oncology R&D, AstraZeneca, in the press release.
The study includes 557 patients across 150 centers worldwide who are being treated with osimertinib monotherapy or osimertinib (80mg once daily oral tablets) with chemotherapy (pemetrexed [500mg/m2] plus cisplatin [75mg/m2] or carboplatin [AUC5]) every 3 weeks for 4 cycles, followed by a maintenance therapy of osimertinib with pemetrexed every 3 weeks.
Annually, approximately 2.2 million people are diagnosed with lung cancer, making it the primary cause of cancer-related death worldwide. NSCLC is the most common form of lung cancer, affecting up to 85% of patients. Approximately 70% of patients with NSCLC are diagnosed with advanced disease and up to 40% of these patients possess EGFRm NSCLC, depending on the region of the world they live in.
No new safety signals were reported in the trial, although more than 2 times the number of patients in the osimertinib/chemotherapy arm experienced grade 3 adverse events (AEs) compared to osimertinib monotherapy (64% and 27%, respectively).
Osimertinib is a third-generation, irreversible EGFR-tyrosine kinase inhibitor (TKI). EFGR-TKIs block cell-signaling pathways responsible for tumor growth, and osimertinib is currently the only targeted therapy that can improve survival among patients with metastatic early- and late-stage EFGRm NSCLC. Investigators are continuing to analyze its benefit for overall survival (OS).Although the OS data is immature, the study investigators note that the treatment combination looks promising.
“We look forward to bringing this potential treatment regimen to patients with advanced lung cancer to further delay disease progression, especially for patients with the greatest unmet need including those with central nervous system metastasis at diagnosis,” Galbraith said in the press release.
Tagrisso plus chemotherapy extended median progression-free survival by nearly 9 months in EGFR-mutated advanced lung cancer in FLAURA2 Phase III trial. AstraZeneca. News Release. September 11, 2023. Accessed September 11, 2023. https://www.astrazeneca.com/media-centre/press-releases/2023/tagrisso-plus-chemotherapy-extended-median-progression-free-survival-by-nearly-9-months-in-egfr-mutated-advanced-lung-cancer-in-flaura2-phase-iii-trial.html