Osimertinib Wins FDA Priority Review in Stage III EGFR+ NSCLC

• The FDA has granted priority review to the supplemental new drug application (sNDA) of osimertinib (Tagrisso) for the treatment of patients with unresectable stage III EGFR-mutated (EGFRm) non–small cell lung cancer (NSCLC) following chemoradiotherapy.
• A decision is expected in the fourth quarter of 2024.
• Priority review is granted to applications of agents that would offer significant improvements to safety or efficacy over existing treatments.

The sNDA of osimertinib for unresectable stage III EGFRm NSCLC following chemoradiotherapy has been granted priority review by the FDA. A Prescription Drug User Fee Act target action date for Q4 of 2024 is expected.¹

The decision is supported by findings from the phase 3 LAURA trial (NCT03521154) that were recently presented at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting.

If approved, osimertinib will be indicated for tumors with exon 19 deletions of exon 21 (L858R) mutations.

“I believe that this will have an immediate impact on management of patients who have stage three locally advanced EGFR-mutated lung cancer, because for these patients, right now, we do chemotherapy and radiation, and we just follow them. The LAURA study had showed that if they don't get any further therapy, within 5 to 6 months, half the patients have disease progression. So, using osimertinib in the setting, a drug that's approved and available for stage IV disease, and it's approved and available for earlier resected lung cancer, would be an easy integration into standard treatment algorithms,” said Suresh Ramalingam, MD, executive director of the Winship Cancer Institute of Emory University, in an interview with Targeted Oncology^TM. Ramalingam presented the data from the LAURA trial at the 2024 ASCO meeting.

Treatment with osimertinib reduced the risk of disease progression or death by 84% compared with placebo (HR, 0.16; 95% CI, 0.10-0.24; P <.001). Patients treated with osimertinib (n = 143) experienced a median progression-free survival (PFS) of 39.1 months (95% CI, 31.5-not calculable) vs 5.6 months (95% CI, 3.7-7.4) for patients who received placebo (n = 73). Further, the 12- and 24-month PFS rates in the osimertinib arm were 74% and 65%, respectively. Those respective rates were 22% and 13% in the placebo arm.²

Regarding safety, the most common any-grade adverse events (AEs) reported in at least 10% of patients included radiation pneumonitis (osimertinib, 48%; placebo, 38%), diarrhea (36%; 14%), rash (24%; 14%), COVID-19 (20%; 8%), paronychia (17%; 1%), cough (16%; 10%), decreased appetite (15%; 5%), dry skin (13%; 5%), pruritus (13%; 7%), stomatitis (12%; 3%), decreased white blood cell count (12%; 3%), pneumonia (11%; 8%), anemia (10%; 4%), and musculoskeletal chest pain (3%; 12%). Grade 3 or higher AEs in the osimertinib arm included pneumonia (3%), radiation pneumonitis (2%), diarrhea (2%), COVID-19 (1%), decreased appetite (1%), dry skin (1%), decreased white blood cell count (1%), and anemia (1%).

In February 2024, the FDA approved osimertinib plus chemotherapy for the treatment of locally advanced or metastatic EGFRm NSCLC based on findings from the phase 3 FLAURA2 trial (NCT04035486).³

REFERENCES:

1. Tagrisso granted priority review in the US for patients with unresectable, stage III EGFR-mutated lung cancer. News release. AstraZeneca. June 10, 2024. Accessed June 10, 2024. https://tinyurl.com/47998c47

2. Ramalingam SS, Kato T, Dong X, et al. Osimertinib (osi) after definitive chemoradiotherapy (CRT) in patients (pts) with unresectable stage (stg) III epidermal growth factor receptor-mutated (EGFRm) NSCLC: primary results of the phase 3 LAURA study. J Clin Oncol. 2024;42(suppl 17):LBA4. doi:10.1200/JCO.2024.42.17_suppl.LBA4

3. FDA approves osimertinib with chemotherapy for EGFR-mutated non-small cell lung cancer. News release. FDA. Updated February 20, 2024. Accessed June 10, 2024. https://tinyurl.com/3afcu4mx