FDA Grants Priority Review to Osimertinib for Adjuvant Treatment of Early-Stage EGFRm NSCLC

The FDA has accepted and granted priority review to the supplemental new drug application (sNDA) for osimertinib (Tagrisso) for the adjuvant treatment of patients with early-stage EGFR-mutated (EGFRm) non-small cell lung cancer (NSCLC) after complete tumor resection with curative intent, according to AstraZeneca, the developer of the agent.¹

The sNDA was based on data observed in the phase 3 ADAURA trial, which showed osimertinib, a third-generation, irreversible EGFR-TKI, demonstrated a statistically significant and clinically meaningful improvement in disease-free survival (DFS) in the study’s primary analysis population of patients with stage II and IIIA EGFRm NSCLC, as well as in the overall trial population of patients with stage IB-IIIA disease, which is a key secondary end point.

The results from the ADAURA trial were presented during the plenary session of the American Society of Clinical Oncology ASCO20 Virtual Scientific Program in May 2020 and were also recently published in The New England Journal of Medicine.²

“Patients with early-stage EGFR-mutated lung cancer are still at considerable risk of recurrence after surgery and adjuvant chemotherapy, and new targeted treatment options are critical to improving outcomes for these patients,” Dave Fredrickson, executive vice president of the Oncology Business Unit at AstraZeneca, said in a press release. “This expedited review underscores the unprecedented disease-free survival benefit [osimertinib] brings to patients in the adjuvant setting, and we will continue working with the FDA to provide this practice-changing treatment to patients as quickly as possible.”

The randomized, double-blinded, global, placebo-controlled, phase 3 trial is focused on the adjuvant treatment of 682 patients with stage IB, II, or IIIA EGFRm NSCLC after complete tumor resection and adjuvant chemotherapy as indicated. Patients were treated with 80 mg oral tablets of osimertinib once daily or placebo for 3 years or until disease recurrence.

Patients enrolled in the trial are from more than 200 centers across more than 20 countries. The primary end point is DFS in stage II and IIIA patients and a key secondary end point is DFS in stage IB, II, and IIIA patients.

Overall, 339 patients were randomized to the osimertinib group and 343 to the placebo group. After 2 years, 90% of the patients with stage II to IIIA disease in the osimertinib group (95% CI, 84-93) and 44% of those in the placebo group (95% CI, 37 to 51) were alive and disease-free (HR, 0.17; 99.06% CI, 0.11-0.26; P < .001). Moreover, in the overall population, 89% of the patients in the osimertinib group (95% CI, 85-92) and 52% of those in the placebo group (95% CI, 46-58) were alive and disease-free after 2 years (HR, 0.20; 99.12% CI, 0.14-0.30; P < .001).

Additionally, 98% of the patients in the osimertinib group (95% CI, 95-99) and 85% of those in the placebo group (95% CI, 80-89) were alive and did not have central nervous system (CNS) disease after 2 years (HR, 0.18; 95% CI, 0.10-0.33). However, overall survival (OS) data were not yet mature at the time of analysis, and the study will continue to assess OS moving forward.

Importantly, 29 patients had died as of the data cutoff, including 9 in the osimertinib group and 20 in the placebo group. No new safety concerns were noted though.

An Independent Data Monitoring Committee recommended for the trial to be unblinded 2 years early in April 2020, based on its determination of overwhelming efficacy. However, investigators and patients continue to participate in the trial and remain blinded to treatment.

In July 2020, the FDA granted breakthrough therapy designation to osimertinib in this setting. The agent is also already approved for both the 1st-line treatment of patients with locally advanced or metastatic EGFRm NSCLC and for the treatment of locally advanced or metastatic EGFR T790M mutation-positive NSCLC in the US, Japan, China, the EU and many other countries around the world.

References:

1. Tagrisso granted Priority Review in the US for the adjuvant treatment of patients with early-stage EGFR-mutated lung cancer [news release]. Published October 20, 2020. Accessed October 20, 2020. https://www.astrazeneca.com/content/astraz/media-centre/press-releases/2020/tagrisso-adjuvant-lung-cancer-us-priority-review.html

2. Wi Y, Tsuboi M, He J, et al. Osimertinib in Resected EGFR-Mutated Non–Small-Cell Lung Cancer. The New England Journal of Medicine. doi: 10.1056/NEJMoa2027071