FDA Grants Priority Review to Osimertinib Plus Chemotherapy for NSCLC

• Osimertinib (Tagrisso) plus chemotherapy has been granted priority review from the FDA for the treatment of patients with locally advanced or metastatic epidermal growth factor receptor-mutated (EGFRm) non­–small cell lung cancer (NSCLC).
• Osimertinib is FDA-approved as a monotherapy for locally advanced or metastatic NSCLC and as an adjuvant therapy for early-stage NSCLC.
• The FDA granted osimertinib monotherapy breakthrough therapy designation in August 2023.

The FDA has accepted a supplemental new drug application and granted priority review for osimertinib in combination with chemotherapy for treatment of patients with locally advanced or metastatic EGFRm NSCLC.

This acceptance is based on the results from the phase 3 FLAURA2 (NCT04035486) trial.¹

Priority review is granted to applications for drugs that would offer significant improvements in safety or efficacy over currently available options. The anticipated action date is during the first quarter of 2024.

“The FLAURA2 results reinforce [osimertinib] as a backbone of standard of care in first line EGRF-mutated non–small cell lung cancer, providing patients with an additional 9 months of media progression-free survival [PFS] when combined with chemotherapy. This option is particularly important for patients with a poorer prognosis such as those with brain metastases. We look forward to working with the FDA on an accelerated timeline to bring this treatment regimen to patients as quickly as possible,” said Susan Galbraith, executive vice president, oncology research and development for AstraZeneca, osimertininb’s manufacturer, in a press release.

Findings from the FLAURA2 trial showed that osimertinib combined with chemotherapy reduced the risk of death or disease progression compared with osimertinib monotherapy by 38% (hazard ratio [HR], 0.62; 95% CI, 0.49-0.79; P =.0001). According to investigator assessment, the combination increased median PFS by 8.8 months compared with osimertinib alone. Results from a blinded independent central review were similar and showed chemotherapy and osimertinib extending median PFS by 9.5 months (HR, 0.62; 95% CI, 0.48-0.80; P =.0002).

Additionally, a clinically significant improvement in PFS was observed across all subgroups, including patients with central nervous system metastases. In this group, osimertinib and chemotherapy decreased the risk of disease progression or death by 53% compared with osimertinib monotherapy (HR, 0.47; 95% CI, 0.33-0.66), and median PFS was extended by 11.1 months.

Data regarding overall survival (OS) were immature, and the safety profile of the combination was generally manageable. More safety information will be released at a later date.¹

The FLAURA2 trial has an enrollment of 587 patients and an estimated completion date of June 2026. The trial’s primary end point is PFS. The secondary end points include OS, landmark OS, objective response rate, duration of response, depth of response, and disease control rate.

Patients in the active comparator arm receive 80 mg of osimertinib administered orally daily. Patients in the experimental arm receive the same dose of osimertininb plus 500 mg/m2 of pemetrexed and 75 mg/m2 of cisplatin or carboplatin on day 1 of a 21-day cycle for 4 cycles. This regimen is followed by daily osimertinib and pemetrexed maintenance every 3 weeks.²

In August 2023, the FDA granted osimertininb with chemotherapy a breakthrough therapy designation for the first-line treatment of adult patients with locally advanced or metastatic EGFRm NSCLC. Osimertinib is approved as a monotherapy in over 100 countries for treatment of patients with locally advanced or metastatic EGFRm NSCLC and locally advanced or metastatic EGFR T790M mutation-positive NSCLC. It is also approved as an adjuvant treatment for early-stage EGFRm NSCLC.¹

REFERENCES:

1. Tagrisso plus chemotherapy granted priority review in the US for patients with EGFR-mutated advanced lung cancer. News release. AstraZeneca. October 16, 2023. Accessed October 16, 2023. https://tinyurl.com/bdcpjzp6

2. A study of osimertinib with or without chemotherapy as 1st line treatment in patients with mutated epidermal growth factor receptor non-small cell lung cancer (FLAURA2). ClinicalTrials.gov. Updated August 2, 2023. Accessed October 16, 2023. https://clinicaltrials.gov/study/NCT04035486