FDA Grants Breakthrough Therapy Designation to Osimertinib for Early-Stage EGFR+ NSCLC

The FDA granted breakthrough therapy designation to osimertinib for the adjuvant treatment of patients with early-stage epidermal growth factor receptor-mutated non-small cell lung cancer after complete tumor resection with curative intent.

The FDA has granted breakthrough therapy designation to osimertinib (Tagrisso) for the adjuvant treatment of patients with early-stage EGFR-mutated non-small cell lung cancer (NSCLC) after complete tumor resection with curative intent, according to AstraZeneca, the developer of the agent.1

The designation was granted based on data from the phase 3 ADAURA trial, which were also recently presented during the plenary session of the 2020 American Society of Clinical Oncology (ASCO) Virtual Scientific Meeting.

“Patients with early-stage EGFR[-mutated] lung cancer often experience recurrence even after successful surgery and adjuvant chemotherapy, yet there are currently no approved targeted treatments to improve outcomes,” José Baselga, executive vice president of Oncology R&D, said in a press release. “The phase 3 ADAURA trial with [osimertinib] demonstrated an unprecedented level of clinical benefit in these patients, and we are working closely with the FDA to deliver this potentially curative treatment to patients as quickly as possible.”

The randomized, double-blinded, global, placebo-controlled phase 3 ADAURA trial evaluated the adjuvant treatment of 682 patients with stage IB, II, IIIA EGFR-mutated NSCLC following complete tumor resection and adjuvant chemotherapy as indicated. In the experimental arm of the study, patients were treated with 80 mg oral tablets of osimertinib once daily for 3 years or until disease recurrence.

The primary end point for the trial was disease-free survival (DFS) in stage II and IIIA patients and a key secondary end point was DFS in stage IB, II, and IIIA patients.

In patients with stage II and IIIA disease, adjuvant treatment with osimertinib reduced the risk of disease recurrence or death by 83% (HR, 0.17; 95% CI, 0.12-0.23; P < 0.0001).2 Moreover, DFS results in the overall trial population (stage IB through IIIA) demonstrated a reduction in the risk of disease recurrence or death by 79% (HR, 0.21; 95% CI, 0.16-0.28; P < 0.0001).

At 2 years, 89% of patients in the trial treated with osimertinib remained alive and disease free versus 53% on placebo. Notably, consistent DFS results were observed across all subgroups, including patients who were treated with surgery followed by chemotherapy and those who received surgery only, as well as in Asian and non-Asian patients.

The data readout was originally anticipated in 2022; however, in April 2020, an independent data monitoring committee recommended for the trial to be unblinded 2 years early based on its determination of overwhelming efficacy. At the time of data cut-off, overall survival (OS) data favored osimertinib, though the data were not mature. The trial will continue to assess OS.

Osimertinib is already approved for the first-line treatment of patients with locally advanced or metastatic EGFR-mutated NSCLC and for the treatment of locally advanced or metastatic EGFR T790M mutation-positive NSCLC in the US, Japan, China, the EU, as well as many other countries around the world. The agent is also being evaluated in the stage III, unresectable setting (LAURA), in the neoadjuvant resectable setting (NeoADAURA), in combination with chemotherapy (FLAURA2), and in combination with potential new medicines to address resistance to EGFR-TKIs (SAVANNAH, ORCHARD).


1. Designation based on unprecedented results from the Phase III ADAURA trial where Tagrisso reduced the risk of disease recurrence or death by c. 80% [news release]. Published July 30, 2020. astrazeneca.com/media-centre/press-releases/2020/tagrisso-us-btd-for-egfrm-adjuvant-lung-cancer.html. Accessed July 30, 2020.

2. Tagrisso demonstrated unprecedented disease-free survival in the adjuvant treatment of Stage IB-IIIA patients with EGFR-mutated lung cancer [news release]. Published May 28, 2020. astrazeneca.com/media-centre/press-releases/2020/tagrisso-demonstrated-unprecedented-disease-free-survival-in-the-adjuvant-treatment-of-stage-ib-iiia-patients-with-egfr-mutated-lung-cancer.html. Accessed July 30, 2020.