FDA Grants Osimertinib Priority Review for Patients With Unresectable, Stage III EGFR-Mutated Lung Cancer


Osimertinib demonstrates improved progression-free survival for stage 3 epidermal growth factor receptor-mutated (EGFRm) lung cancer.

Osimertinib (Tagrisso; AstraZeneca) was given priority review by the FDA after positive results from the LAURA phase 3 trial (NCT03521154) showed significant improvement in progression free survival (PFS) for patients with unresectable, stage 3 epidermal growth factor receptor-mutated (EGFRm) non-small cell lung cancer (NSCLC) whose tumors have exon 19 deletions or exon 21 (L858R) mutations, after chemoradiotherapy (CRT) compared with placebo after CRT. The findings indicate the potential for osimertinib as a standard-of-care (SoC) treatment for EGFRm NCSLC, underscoring the need for early testing and diagnosis in patients.

3d image of lungs with lung cancer, non-small cell lung cancer, oncology

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Every year, an estimated 2.4 million individuals globally are diagnosed with lung cancer, of which 80% to 85% are diagnosed with NSCLC, the most common form of the disease. SoC treatment for patients with EGFRm NSCLC are EGFR-tyrosine kinase inhibitors (EGFR-TKI), which block the activity of mutated EGFR proteins to slow tumor growth. Most recently, studies investigating use of osimertinib showed significant success in extending PFS to improve patient outcomes for early stage, locally advanced, and late-stage disease.1

Osimertinib is a third-generation tyrosine kinase inhibitor (TKI) oral therapy used to target mutations in the EGFR gene, which is involved in cell growth and survival in NSCLC. It has been routinely used for EGFRm advanced/metastatic NSCLC with recent success as an adjuvant treatment for resectable EGRFm NSCLC.1-3

The double-blind, placebo-controlled trial included 216 participants across 145 centers globally with unresectable stage 3 EGFRm NSCLC who have L858R mutations after chemoradiotherapy (CRT). The patients were randomly assigned to receive 80 mg daily of osimertinib (n=143) or placebo (n=73) until disease progression or discontinuation of treatment occurred. The primary end point of the study was PFS, which was assessed by blinded independent central view.1,2,4

The study findings showed that osimertinib results in significant PFS compared with placebo, demonstrating a median survival of 39.1 months (hazard ratio [HR] 0.16; 95% confidence interval [CI], 0.10 to 0.24; P<.001). Additionally, 74% (95% CI, 65-80) of patients taking osimertinib were alive and progression free compared with 22% (95% CI, 13-32) of patients taking placebo. Interim overall survival (OS) data (maturity, 20%) showed 36-month OS among 84% of patients with osimertinib (95% CI, 75 to 89) and 74% with placebo (95% CI, 57 to 85), with a HR for death of 0.81 (95% CI, 0.42 to 1.56; P=.53).1,2,4

The study authors observed adverse events (AEs) of grade 3 or higher in 35% of patients in the osimertinib group and 12% in the placebo group, including radiation pneumonitis (majority grade 1 to 2) which was reported in 48% and 38%, respectively.1,2,4

Osimertinib is being investigated in further studies, including as a neoadjuvant setting in the NeoADURA phase 3 trial (NCT04351555) and in the early-stage adjuvant resectable setting in the ADURA2 phase 3 trial (NCT02511106). Additionally, researchers are investigating osimertinib in conjunction with savolitinib (Orpathys; AstraZeneca), a highly selective, potent MET TKI, as a way to address tumor mechanisms of resistance.1

“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,” Suresh Ramalingam, MD, Executive Director of Winship Cancer Institute of Emory University, Atlanta, US, said in a news release. “Osimertinib delayed the risk of disease progression or death by an unprecedented 84% and should become the new [SoC] for patients in this setting based on these data.”1

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. AstaZeneca. June 2, 2024. Accessed June 10, 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. Lu S, Kato T, Dong X, et al. Osimertinib after chemoradiotherapy in stage III EGFR-mutated NSCLC. NEJM. June 2, 2024. DOI: 10.1056/NEJMoa2402614
3. EGFR gene. National Cancer Institute. February 2, 2011. Accessed June 10, 2024. https://www.cancer.gov/publications/dictionaries/cancer-terms/def/egfr-gene
4. Osimertinib New Standard of Care for Stage 3, EGFRm NSCLC. Pharmacy Times. June 2, 2024. Accessed June 10, 2024. https://www.pharmacytimes.com/view/osimertinib-new-standard-of-care-for-stage-3-egfrm-nsclc

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