Osimertinib Receives FDA Breakthrough Therapy Designation for Adjuvant Treatment of Early-Stage EGFR-Mutated NSCLC

Source | Jike Yaowen

On July 30, AstraZeneca announced that osimertinib (Tagrisso) has received Breakthrough Therapy Designation (BTD) in the United States for adjuvant curative treatment of patients with early-stage (IB, II, and IIIA) epidermal growth factor receptor-mutated (EGFRm) non-small cell lung cancer (NSCLC) following complete resection. This BTD designation is based on the striking results from the Phase 3 ADAURA trial, in which Tagrisso reduced the risk of disease recurrence or death by approximately 80%.

Although up to 30% of patients with non-small cell lung cancer (NSCLC) can be diagnosed at an early stage and undergo potentially curative surgery, disease recurrence is common in early-stage disease; nearly half of patients diagnosed at stage IB and more than three-quarters of those diagnosed at stage IIIA experience recurrence within five years.

José Baselga, Executive Vice President of Oncology R&D at AstraZeneca, said, “Patients with early-stage EGFRm lung cancer often experience recurrence even after successful surgery and adjuvant chemotherapy; however, there are currently no approved targeted therapies to improve prognosis. The Phase 3 clinical trial of Tagrisso (ADAURA) demonstrated an unprecedented level of clinical benefit in these patients. We are working closely with the FDA to make this potentially curative treatment available to patients as soon as possible.”

The breakthrough therapy designation is based on data from the Phase 3 clinical trial (ADAURA), which were recently presented at the 2020 American Society of Clinical Oncology (ASCO) Annual Meeting. ADAURA is a global, randomized, double-blind, placebo-controlled Phase 3 clinical trial that enrolled 682 patients with stage IB, II, or IIIA EGFR-mutated non-small cell lung cancer (EGFRm NSCLC) who had previously undergone complete resection and adjuvant chemotherapy. In the experimental arm, patients received Tagrisso as an 80 mg oral tablet once daily for three years or until disease recurrence. The trial demonstrated that Tagrisso, as adjuvant therapy for patients with stage IB–IIIA EGFRm NSCLC, achieved a statistically significant and clinically meaningful improvement in disease-free survival (DFS). Among key secondary endpoints, it reduced the risk of disease recurrence or death by 79% (hazard ratio [HR] 0.21; 95% confidence interval [CI] 0.16–0.28; p<0.0001). In April 2020, the independent data monitoring committee recommended unblinding the trial two years ahead of schedule due to the overwhelming efficacy observed. Although clinical data results were initially expected in 2022, the trial will continue to evaluate overall survival (OS).

Osimertinib (osimertinib, Tagrisso) is a third-generation, irreversible EGFR-TKI with clinical activity against CNS metastases. Once-daily oral Tagrisso tablets at doses of 40 mg and 80 mg have been approved in the United States, Japan, China, the European Union, and many other countries worldwide for the first-line treatment of locally advanced or metastatic EGFRm NSCLC, as well as for patients with locally advanced or metastatic EGFR T790M mutation-positive NSCLC. Tagrisso is also under development in Phase 3 clinical trials in the unresectable setting (LAURA), the neoadjuvant resectable setting (NeoADAURA), in combination with chemotherapy (FLAURA2), and in combination with potential novel agents to address EGFR-TKI resistance (SAVANNAH, ORCHARD).

References:

[1] Tagrisso granted Breakthrough Therapy Designation in the US for the adjuvant treatment of patients with Stage IB-IIIA EGFR-mutated lung cancer. Retrieved 2020-07-30, from https://www.astrazeneca.com/media-centre/press-releases/2020/tagrisso-us-btd-for-egfrm-adjuvant-lung-cancer.html

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