Frontline Osimertinib Approved in Japan for NSCLC

The Japanese Ministry of Health, Labour, and Welfare (MHLW) has approved osimertinib for the frontline treatment of patients with inoperable or recurrent EGFR-positive non–small cell lung cancer.

Dave Fredrickson

The Japanese Ministry of Health, Labour, and Welfare (MHLW) has approved osimertinib (Tagrisso) for the frontline treatment of patients with inoperable or recurrent EGFR-positive non—small cell lung cancer (NSCLC), according to AstraZeneca, the manufacturer of the EGFR inhibitor.

The approval is based on the phase III FLAURA study, in which frontline osimertinib reduced the risk of disease 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 PFS benefit with osimertinib extended across subgroups defined by race (Asian vs non-Asian), EGFR mutation type (exon 19 del vs L858R), and the presence or absence of CNS metastases at baseline.

“Tagrisso is already approved in Japan for the treatment of patients with EGFR T790M mutation—positive inoperable or recurrent NSCLC that is resistant to existing first-line EGFR-inhibitor medicines. Today’s approval moves the use of Tagrisso to the first-line setting, replacing older medicines which, given the high prevalence of the EGFR mutation in Japan, offers an important new treatment option for these patients,” Dave Fredrickson, Executive Vice President, Head of the Oncology Business Unit, AstraZeneca, 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 objective response rate with osimertinib was 80% compared with 76% for erlotinib and gefitinib (OR, 1.27; 95% CI, 0.85-1.90; P = .24). The median duration of response was 17.2 months (95% CI, 13.8-22.0) versus 8.5 months (95% CI, 7.3-9.8), respectively.

Medians had not yet been reached for overall survival (OS), 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 = .007). However, those results have not yet been shown to be statistically significant. The 18-month OS rate was 83% with osimertinib versus 71% in the comparator cohort.

Grade ≥3 adverse events (AEs) occurred in 34% of the osimertinib arm versus 45% of the comparator arm. The most frequently reported all-grade AEs reported for patients receiving osimertinib were rash/acne (54.5%), diarrhea (49.5%), dry skin/eczema (33.3%) and nail disorder including paronychia (32.6%).

In the United States, the FDA approved osimertinib in April 2018 as a first-line treatment for patients with NSCLC whose tumors harbor EGFR mutations (exon 19 deletions or exon 21 L858R substitution mutations). According to AstraZeneca, 40 countries have now approved osimertinib for the first-line treatment of patients with EGFR mutation—positive NSCLC.

Soria JC, Ohe Y, Vansteenkiste J, et al. Osimertinib in Untreated EGFR-Mutated Advanced Non-Small-Cell Lung Cancer. N Engl J Med. 2018;378(2):113125. doi: 10.1056/NEJMoa1713137.