Osimertinib Granted Breakthrough Status for Early-Stage, EGFR-Mutated NSCLC Patients After Surgery

July 31, 2020

The ADAURA trial was stopped in April 2020 after an independent monitoring committee called for the trial to be unblinded 2 years early based on a determination of overwhelming efficacy.

AstraZeneca reported July 30 that osimertinib, sold as Tagrisso, has been granted Breakthrough Therapy Designation (BTD) from FDA for adjuvant treatment of patients with early-stage, epidermal growth factor–mutated (EGFRm) non–small cell lung cancer (NSCLC), following surgery for completely tumor resection.

The action follows a presentation during the 2020 American Society of Clinical Oncology (ASCO) virtual meeting of the ADAURA trial, which showed that treatment with osimertinib reduced the risk of disease recurrence or death by 79% (hazard ratio .21, 95% CI 0.16-0.28; P < .0001) in a key secondary end point. The ADAURA trial was stopped in April 2020 after an independent monitoring committee called for the trial to be unblinded 2 years early based on a determination of overwhelming efficacy.

Osimertinib, a third-generation, irreversible EGFR tyrosine kinase inhibitor, is already the preferred option for patients with advanced EGFRm NSCLC. Following presentation of the ADAURA results, both the study’s lead author and commentators said osimertinib should also become the treatment of choice for patients with EGFRm who are treated after surgery for early-stage, localized disease (stage IB-IIIA). The EGFRm genetic driver is seen in 10% to 15% of NSCLC cases in the United States and up to 40% of cases in Asia.

With current treatments, nearly half of patients diagnosed in stage IB experience disease recurrence, and more than three-fourths of patients diagnosed in stage IIIA experience recurrence within 5 years.

"Patients with early-stage EGFRm 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 for Oncology R&D at AstraZeneca, said in a statement. "The phase 3 ADAURA trial with Tagrisso 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."

BTD is a process that expedites review of drugs that may offer substantial improvement over available therapy on clinical end points that include irreversible morbidity or mortality or serious symptoms.