FDA Approves Tagrisso for EGFR-Mutated Non-Small Cell Lung Cancer Based on Phase III FLAURA 2 Trial Data

Image credit: SciePro | stock.adobe.com. 3d rendered illustration of lung cancer 3D illustration

The FDA has approved AstraZeneca’s Tagrisso (osimertinib) for use in combination with platinum-based chemotherapy in adults with locally advanced or metastatic epidermal growth factor receptor-mutated (EGFRm) non-small cell lung cancer (NSCLC) harboring EGFR exon 19 deletions or exon 21 L858R mutations, as detected by an FDA-approved test.^1,2 Tagrisso was previously approved as a monotherapy for the first-line treatment of patients with locally advanced or metastatic EGFRm NSCLC, locally advanced or metastatic EGFR T790M mutation-positive NSCLC, and adjuvant treatment of early-stage EGFRm NSCLC.

“This important new treatment option can delay disease progression by nearly nine additional months, establishing a new benchmark with the longest reported progression-free survival benefit in the 1st-line advanced setting,” said Dave Fredrickson, executive vice president, Oncology Business Unit, AstraZeneca, in a press release. “This approval reinforces Tagrisso as the backbone of EGFR-mutated lung cancer treatment either as monotherapy or in combination with chemotherapy. This news is especially important for those with a poorer prognosis, including patients whose cancer has spread to the brain and those with L858R mutations.”¹

Tagrisso is a tyrosine kinase inhibitor of the EGFR domain that binds irreversibly to these specific forms of EGFR mutants at approximately nine times greater relative ligand potency than wild type. This action selectively inhibits EGFR-meditated uncontrolled growth of cancer cells and cell signaling, leading to reduced tumor growth and spread.³

The latest approval was based on data from the randomized, multicenter, open-label, Phase III FLAURA 2 trial (NCT04035486). Investigators enrolled patients with locally advanced or metastatic NCSLC harboring an EGFR exon 19 deletion or exon 21 L858R mutation who were not previously administered a systemic treatment for advanced disease.

The trial's primary endpoint was progression-free survival (PFS) as assessed by investigators and RECIST v1.1 criteria. The trial’s key secondary endpoint was overall survival (OS), with other key endpoints that included objective response rate (ORR) and duration of response (DOR).

Patients administered Tagrisso plus chemotherapy (n = 279) experienced significantly improved PFS compared with Tagrisso monotherapy (n = 278), with a median of 25.5 months compared with 16.7 months, respectively. At the time of the current analysis, OS data were not yet mature, with 45% of prespecified deaths reported.

The Tagrisso combination produced an ORR of 77% compared with 69% in the Tagrisso monotherapy cohort. Median DOR for the combination cohort was 24.9 months compared to 17.9 months in the monotherapy cohort. Median duration of exposure in the Tagrisso cohort was 22.3 months compared with 19.3 months in the monotherapy cohort.

In terms of safety, serious adverse events (AEs) were reported in 38% of patients administered the Tagrisso combintion, with 7% of patients experiencing fatal toxicities. AEs caused dose interruptions or reductions in 44% of patients administered the Tagrisso combination compared with 10% of patients in the monotherapy cohort, with 11% having AEs that led to treatment discontinuation.

The most common AEs observed in 10% or more of patients administered Tagrisso plus chemotherapy were diarrhea (any grade, 43%; grade ≥3, 2.9%), stomatitis (31%; 0.4%), rash (49%; 2.5%), nail toxicity (27%; 0.7%), dry skin (24%; 0%), and pruritus (8%; 0%).

“This approval based on the unprecedented data from FLAURA2 brings a critical new treatment option to patients with advanced EGFR-mutated non-small cell lung cancer. Now, with the choice of two highly effective osimertinib-based options, physicians can better tailor treatment to an individual’s needs and help ensure the best possible outcome for each patient,” said FLAURA 2 trial principal investigator Pasi A. Jänne, MD, PhD, medical oncologist at Dana-Farber Cancer Institute, in the release.¹

References

1. Tagrisso with the addition of chemotherapy approved in the US for patients with EGFR-mutated advanced lung cancer. AstraZeneca. News release. February 19, 2024. Accessed February 19, 2024. https://www.astrazeneca.com/media-centre/press-releases/2024/tagrisso-plus-chemo-approved-in-us-for-lung-cancer.html

2. FDA approves osimertinib with chemotherapy with chemotherapy for EGFR-mutated non-small cell lung cancer. FDA. February 16, 2024. Accessed February 19, 2024. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-osimertinib-chemotherapy-egfr-mutated-non-small-cell-lung-cancer

3. Tagrisso. Prescribing information. AstraZeneca Pharmaceuticals LP; 2024. Accessed February 19, 2024. https://www.accessdata.fda.gov/drugsatfda_docs/label/2024/208065s030lbl.pdf