Frontline Osimertinib Approved in China for EGFR+ NSCLC

Dave Fredrickson

China’s National Medical Products Administration has approved osimertinib (Tagrisso) for the frontline treatment of adult patients with locally-advanced or metastatic non—small cell lung cancer (NSCLC) whose tumors harbor EGFR exon 19 deletions or exon 21 (L858R) substitutions.

The approval is based on the phase III FLAURA trial , in which frontline osimertinib reduced the risk of progression or death by 54% versus standard TKI therapy—erlotinib (Tarceva) or gefitinib (Iressa). In the double-blind study, the median progression-free survival (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).

“The FLAURA trial has demonstrated the potential of Tagrisso as a new standard of care and as an important new 1st-line treatment option for non-small cell lung cancer patients in China, where approximately 30% to 40% are diagnosed with an EGFR mutation—more than any other country in the world,” Dave Fredrickson, executive vice President, oncology, AstraZeneca, the manufacturer of osimertinib, said in a statement.

In the FLAURA trial, 556 treatment-naïve patients with EGFR-positive locally advanced or metastatic NSCLC 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.

Medians had not yet been reached for overall survival, but at just 25% maturity, HR favored osimertinib at 0.63, a 37% reduction in the risk of death (95% CI, 0.45-0.88; P = .0068). However, those results have not yet been shown to be statistically significant. At the time of the analysis, there had been 58 deaths in the osimertinib arm and 83 in the control group.

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%).

Osimertinib was previously approved in the United States and Europe for the frontline treatment of patients with EGFR-positive NSCLC.

Ramalingam S, Reungwetwattana T, Chewaskulyong B, et al. Osimertinib vs standard of care (SoC) EGFR-TKI as first-line therapy in patients (pts) with EGFRm advanced NSCLC: FLAURA. Presented at: 2017 ESMO Congress; Madrid, Spain; September 9-12, 2017. Abstract LBA2_PR.