AstraZeneca Korea's Tagrisso (osimertinib) has expanded its indication to include the first-line treatment of EGFR-mutated non-squamous NSCLC.

The Ministry of Food and Drug Safety on Monday approved Tagrisso in combination with pemetrexed and platinum-based chemotherapy for the first-line treatment of locally advanced or metastatic EGFR-mutated NSCLC with EGFR exon 19 deletion or exon 21 (L858R) substitution.

The approval expanded Tagrisso-based treatment options to include Tagrisso monotherapy and Tagrisso in combination with anticancer chemotherapy for the first-line treatment of patients with locally advanced or metastatic EGFR-mutant NSCLC with EGFR exon 19 deletion or exon 21 (L858R) substitution..

Tagrisso, in combination with anticancer chemotherapy, was granted priority review designation by the U.S. Food and Drug Administration (FDA) in October of last year for treating locally advanced or metastatic NSCLC with EGFR exon 19 deletion or exon 21 L858R mutation and was approved by the FDA in February.

The Korean regulator’s approval of the Tagrisso-anticancer chemotherapy combination was based on the FLAURA2 trial, which was presented at the World Conference on Lung Cancer by the International Association for the Study of Lung Cancer last year (IASLC 2023 WCLC) and published in The New England Journal of Medicine the same year.

FLAURA2 was a phase 3 trial comparing the efficacy of Tagrisso-anticancer chemotherapy with Tagrisso vs. Tagrisso alone in patients with EGFR mutation-positive locally advanced or metastatic non-squamous NSCLC.

Results showed that the Tagrisso-anticancer chemotherapy combination reduced the risk of disease progression or death by 38 percent compared to Tagrisso monotherapy (HR 0.62; 95 percent CI 0.49-0.79; p<0.001). Median investigator-assessed progression-free survival (mPFS) was 25.5 months, an 8.8-month extension compared to Tagrisso monotherapy (16.7 months). Median PFS by independent blinded centralized review (BICR) was 29.4 months, longer than Tagrisso alone (19.9 months) (HR 0.62; 95 percent CI 0.48-0.80).

In this trial, the Tagrisso-antineoplastic chemotherapy combination reduced the risk of disease progression or death from central nervous system (CNS) metastases by 42 percent compared to Tagrisso monotherapy (HR 0.58; 95 percent CI 0.33-1.01; p=0.0548 based on BICR). In patients with CNS metastases, mPFS was 11.1 months longer with the Tagrisso-antineoplastic chemotherapy combination (24.9 months) than with Tagrisso alone (13.8 months) (HR 0.47; 95 percent CI 0.33-0.66).

In patients with the L858R mutation, the Tagrisso-anti-cancer chemotherapy combination (24.7 months) was 10.8 months longer than Tagrisso monotherapy (13.9 months), confirming a consistent benefit in patients with greater unmet needs, such as CNS metastases or the L858R mutation.

"The treatment of patients with EGFR-mutant NSCLC with brain metastases or L858R-substituted variants is challenging, and their prognosis is poor," said Professor Kim Sang-we of the Department of Medical Oncology at Asan Medical Center, the Korean principal investigator of the FLAURA2 study. “With unmet medical needs in these patients, the clinical utility of the Tagrisso-anti-cancer chemotherapy combination has been confirmed in the FLAURA2 study."

Professor Kim continued, “The approval of Tagrisso in combination with anticancer chemotherapy in Korea is significant because it means that patients with EGFR-mutated NSCLC will now have a choice between two effective first-line treatment options based on Tagrisso.”