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Osimertinib and chemotherapy is more effective than osimertinib alone as first-line treatment for patients with EGFR-mutant, advanced non-small cell lung cancer (NSCLC), according to research presented at the 2023 World Conference on Lung Cancer.
Results from this phase 3 study, FLAURA2, revealed a higher response rate and longer progression-free survival (PFS) with osimertinib plus platinum-pemetrexed chemotherapy.
The FLAURA2 study (ClinicalTrials.gov Identifier: NCT04035486) enrolled patients with EGFR-mutant, advanced NSCLC who had received no prior treatment for advanced disease. The patients were randomly assigned to receive osimertinib plus chemotherapy (276 treated) or osimertinib alone (275 treated). Baseline characteristics were generally well balanced between the arms.
Patients received osimertinib (80 mg once daily) plus pemetrexed (500 mg/m2 on day 1) and cisplatin (75 mg/m2 on day 1) or carboplatin (AUC 5 on day 1) every 3 weeks for 4 cycles, or osimertinib monotherapy (80 mg once daily). This was followed by maintenance with daily osimertinib and pemetrexed every 3 weeks or daily osimertinib alone until progression or discontinuation.
The objective response rate was 83% in the osimertinib-chemotherapy arm and 76% in the osimertinib monotherapy arm. The median duration of response was 24.0 months and 15.3 months, respectively.
Per investigator assessment, the median PFS was 25.5 months in the osimertinib-chemotherapy arm and 16.7 months in the osimertinib monotherapy arm (hazard ratio [HR], 0.62; 95% CI, 0.49-0.79; P <.0001). The 1-year PFS rate was 80% in the combination arm and 66% in the monotherapy arm. The 2-year PFS rates were 57% and 41%, respectively.
Per blinded independent review, the median PFS was 29.4 months in the osimertinib-chemotherapy arm and 19.9 months in the osimertinib monotherapy arm (HR, 0.62; 95% CI, 0.48-0.80; P =.0002). The 1-year PFS rate was 80% in the combination arm and 67% in the monotherapy arm. The 2-year PFS rates were 62% and 47%, respectively.
The PFS benefit with osimertinib and chemotherapy was consistent across all predefined subgroups, according to study presenter Pasi Janne, MD, PhD, of the Dana Farber Cancer Institute in Boston.
He noted that, among patients with central nervous system (CNS) metastasis, the median PFS per investigator was 24.9 months in the combination arm and 13.8 months in the monotherapy arm (HR, 0.47; 95% CI, 0.33-0.66). Among patients without CNS metastasis, the median PFS per investigator was 27.6 months in the combination arm and 21.0 months in the monotherapy arm (HR, 0.75; 95% CI, 0.55-1.03).
Dr Janne also noted that second PFS (PFS2) and overall survival (OS) data were both immature. However, the median PFS2 was 30.6 months in the combination arm and 27.8 months in the monotherapy arm (HR, 0.70; 95% CI, 0.52-0.93; P =.0132). The median OS was not reached in either arm (HR, 0.90; 95% CI, 0.65-1.24; P =.5238)
The rate of adverse events (AEs) possibly related to treatment was 97% in the combination arm and 88% in the monotherapy arm. The rate of grade 3 or higher AEs possibly related to treatment was 53% and 11%, respectively.
The most common AEs in the combination arm were anemia, diarrhea, nausea, and neutropenia. The most common AEs in the monotherapy arm were diarrhea, paronychia, dry skin, and rash. The rate of interstitial lung disease was 3% in the combination arm and 4% in the monotherapy arm.
Based on these results, Dr Janne concluded that osimertinib plus platinum-pemetrexed chemotherapy could be a new first-line treatment option for patients with EGFR-mutant, advanced NSCLC.
Disclosures: This research was supported by AstraZeneca. Dr Janne disclosed relationships with AstraZeneca, Astellas Pharmaceuticals, Biocartis, Boehringer Ingelheim, ACEA Biosciences, Araxes, Bayer, Chugai Pharmaceuticals, Daiichi Sankyo, Eli Lilly, Eisai, Gatekeeper Pharmaceuticals, Ignyta, Labcorp, Mirati Therapeutics, Novartis, Nuvalent, Pfizer, PUMA, Revolution Medicines, Roche/Genentech, Sanofi, SFJ Pharmaceuticals, Silicon Therapeutics, Syndax, Takeda Oncology, Transcenta, and Voronoi.
Reference
Janne P, Planchard D, Cheng Y, et al. Osimertinib with/without platinum-based chemotherapy as first-line treatment in patients with EGFRm advanced NSCLC (FLAURA2). Presented at WCLC 2023. September 9-12, 2023. Abstract PL03.13.
This article originally appeared on Cancer Therapy Advisor
