Tagrisso Shows Significant Improvement in Progression-Free Survival in EGFRm NSCLC in Phase III Trial

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Treatment with Tagrisso (osimertinib; AstraZeneca) produced a statistically significant and clinically meaningful improvement in progression-free survival (PFS) among patients with unresectable, stage III epidermal growth factor receptor-mutated (EGFRm) non-small cell lung cancer (NSCLC) with tumors that harbor exon 19 deletions or exon 21 (L858R) mutations, following chemoradiotherapy (CRT) in comparison to placebo following CRT. These data from the Phase III LAURA trial, released at the 2024 American Society of Clinical Oncology Annual Meeting, show the therapy lowered the risk of disease progression or death by 84% vs. placebo (hazard ratio [HR] 0.16; 95% confidence interval [CI] 0.10-0.24; p<0.001).¹

“Tagrisso extended [PFS] by more than three years in this potentially curative setting, reinforcing the need to test and diagnose patients early,” Susan Galbraith, executive vice president, Oncology R&D, AstraZeneca, said in a press release. “These practice-changing data cement the powerful impact Tagrisso can make as backbone therapy in EGFR-mutated lung cancer, especially in the lives of these patients who have historically experienced early progression following [CRT].”¹

Tagrisso is a tyrosine kinase inhibitor of the EGFR domain that binds irreversibly to 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.²

Earlier this year, Tagrisso was approved by the FDA for use in combination with platinum-based chemotherapy in adults with locally advanced or metastatic EGFRm NSCLC harboring EGFR exon 19 deletions or exon 21 L858R mutations, as detected by an FDA-approved test.^3,4 Tagrisso has also been 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.

The randomized, double-blind, placebo-controlled, multi-center, global LAURA trial enrolled 216 patients with unresectable, stage III EGFRm NSCLC whose disease did not progress after treatment with definitive platinum‑based CRT. Patients were administered oral Tagrisso at a dose of 80 mg once daily until disease progression, unacceptable toxicity, or reaching other discontinuation criteria. Following disease progression, patients in the placebo cohort were allowed to switch to treatment with Tagrisso. The trial’s primary endpoint is PFS, with the analysis ongoing to evaluate the secondary endpoint of overall survival (OS).

Median PFS in the Tagrisso cohort was 39.1 months compared with 5.6 months in the placebo cohort. Investigators noted that Tagrisso produced a clinically meaningful PFS benefit across all prespecified subgroups, including sex, race, EGFR mutation type, age, smoking history, and prior administration of CRT. While OS data favored Tagrisso, the findings were not mature at the time of the analysis.

In terms of safety, no new safety signals were reported, with grade 3 or higher adverse events from all causes observed in 35% of patients administered Tagrisso compared with 12% of patients in the placebo cohort.

“The impressive [PFS] results from the LAURA Phase III trial represent a major breakthrough for patients with stage III EGFR-mutated lung cancer for whom no targeted treatments are available,” principal trial investigator Suresh Ramalingam, MD, executive director of Winship Cancer Institute of Emory University, said in the press release. “[Tagrisso] delayed the risk of disease progression or death by an unprecedented 84% and should become the new standard of care for patients in this setting based on these data.”¹

References

1. Tagrisso reduced the risk of disease progression or death by 84% in patients with unresectable, Stage III EGFR-mutated lung cancer vs. placebo in LAURA Phase III trial. News release. AstraZeneca. June 2, 2024. Accessed June 4, 2024. https://www.astrazeneca.com/media-centre/press-releases/2024/tagrisso-reduced-the-risk-of-disease-progression-or-death-by-84-percent-in-patients-with-unresectable-stage-iii-egfr-mutated-lung-cancer-vs-placebo.html#!

2. Tagrisso. Prescribing information. AstraZeneca Pharmaceuticals LP; 2024. Accessed June 4, 2024. https://www.accessdata.fda.gov/drugsatfda_docs/label/2024/208065s030lbl.pdf

3. 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 June 4, 2024. https://www.astrazeneca.com/media-centre/press-releases/2024/tagrisso-plus-chemo-approved-in-us-for-lung-cancer.html

4. FDA approves osimertinib with chemotherapy with chemotherapy for EGFR-mutated non-small cell lung cancer. FDA. February 16, 2024. Accessed June 4, 2024. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-osimertinib-chemotherapy-egfr-mutated-non-small-cell-lung-cancer