Frontline osimertinib significantly improved overall survival compared with erlotinib or gefitinib in patients with EGFR-positive local advanced or metastatic non–small cell lung cancer, according to results from the phase III FLAURA trial.
José Baselga, MD
Frontline osimertinib (Tagrisso) significantly improved overall survival (OS) compared with erlotinib (Tarceva) or gefitinib (Iressa) in patients with EGFR-positive local advanced or metastatic non—small cell lung cancer (NSCLC), according to results from the phase III FLAURA trial.1
Based on previously reported progression-free survival (PFS) data from FLAURA, the FDA approved osimertinib in April 2018 for use in this setting. AstraZeneca, the manufacturer of the third-generation EGFR inhibitor, reported in a press release that the OS data will be presented at an upcoming medical conference.
“Today’s positive results show that Tagrisso provides an unprecedented survival outcome versus previous standard-of-care epidermal growth factor receptor tyrosine kinase inhibitors, reaffirming Tagrisso as the first-line standard-of-care for EGFR-mutated metastatic non—small cell lung cancer,” José Baselga, MD, PhD, executive vice president, Oncology R&D, AstraZeneca, said in the press release.
In FLAURA, frontline osimertinib reduced the risk of progression or death by 54% versus erlotinib or gefitinib. In the double-blind study, the median PFS was 10.2 months (95% CI, 9.6-11.1) for standard therapy and 18.9 months (95% CI, 15.2-21.4) with osimertinib (HR, 0.46; 95% CI, 0.37-0.57; P <.0001).2
The FLAURA trial included 556 treatment-naïve patients with EGFR-positive locally advanced or metastatic NSCLC who were randomly assigned to osimertinib (n = 279) or a standard TKI (erlotinib or gefitinib; n = 277). Patients with CNS metastases were allowed on the trial and all patients had exon 19 deletions or L858R mutations. Daily oral therapy was given with 80 mg of osimertinib, 250 mg of gefitinib, or 150 mg of erlotinib.
The PFS benefit with osimertinib extended across all prespecified subgroups. In patients with CNS metastases (n = 116), the median PFS with osimertinib was 15.2 months (95% CI, 12.1-24.4) compared with 9.6 months (95% CI, 7.0-12.4) with standard therapy (HR, 0.47; 95% CI, 0.30-0.74; P = .0009). In those without CNS involvement (n = 440), the median PFS was 19.1 months (95% CI, 15.2-23.5) and 10.9 months (95% CI, 9.6-12.3), for osimertinib and the control arm, respectively (HR, 0.46; 95% CI, 0.36-0.59; P <.0001). Across all patients, CNS progression occurred in 6% treated with osimertinib versus 15% for erlotinib and gefitinib.
The objective response rate with osimertinib was 77% compared with 69% for erlotinib and gefitinib. The median duration of response with osimertinib was 17.6 months versus 9.6 months in the comparator arm.
The most common all-grade adverse events (AEs) were diarrhea (58%) and dry skin (32%) in the experimental group compared with diarrhea (57%) and dermatitis acneiform (48%) in the control group.
Overall, 33.7% of patients experienced a grade ≥3 AE in the osimertinib group compared with 44.8% for erlotinib and gefitinib. Patients in the osimertinib group were less likely to discontinue treatment because of AEs (13.3% vs 18.1%).
The FDA granted osimertinib an accelerated approval in November 2015 followed by a full indication in March 2017 for patients with EGFR T790M—positive NSCLC whose disease progressed on or after EGFR TKI therapy.