NEW YORK – The US Food and Drug Administration approved osimertinib (AstraZeneca's Tagrisso) on Friday as an adjuvant treatment for EGFR-mutated non-small cell lung cancer patients.
This marks the first time the FDA has approved an adjuvant treatment for a genomically defined subset of patients with NSCLC. The agency made its decision based on the results of the Phase III ADAURA trial, in which 682 NSCLC patients with EGFR exon 19 deletions or exon 21 L8558R mutations were randomized to receive osimertinib or placebo after surgical removal of their tumors and adjuvant chemotherapy. Treatment with osimertinib decreased the risk of cancer recurrence or death by 80 percent compared to those on placebo.
Patients in the study had stage Ib to III disease and their tumor mutation status was determined by Roche's cobas EGFR Mutation Test in a central lab. Researchers were primarily interested in median disease-free survival in patients with stage II to IIIA tumors, which was not reached in the osimertinib arm and 19.6 months in the placebo arm. In the overall population, median disease-free survival was again not reached in the osimertinib arm and 27.5 months in the placebo arm.
The ADAURA trial was unblinded early after an independent data monitoring committee determined that adjuvant osimertinib demonstrated "overwhelming efficacy" based on the disease-free survival endpoint. However, oncologists were divided as to whether the disease-free survival data, in the absence of mature overall survival data, was sufficient evidence of adjuvant osimertinib's benefit in this setting.
Despite the debate in the oncology community, the FDA approved the treatment, giving a subset of NSCLC patients the opportunity to receive personalized treatment earlier in their treatment trajectory. Osimertinib is already approved as a first-line treatment for metastatic NSCLC patients with common EGFR mutations, including the T790M resistance mutation.
"Today's approval of Tagrisso demonstrates how additional research on therapies approved in later stages of cancer can eventually improve treatment options for patients in earlier stages," Richard Pazdur, director of the FDA's Oncology Center of Excellence, said in a statement. "With this approval, patients may be treated with this targeted therapy in an earlier and potentially more curative stage of non-small cell lung cancer."
Three-fourths of nearly 230,000 new lung cancer diagnoses in the US this year will be non-small cell lung cancers. Given that 20 percent of NSCLC patients harbor EGFR mutations and 30 percent are eligible for surgical resection of their tumors, the agency estimates that around 10,000 patients will be eligible each year for adjuvant osimertinib.
Osimertinib has orphan drug designation and breakthrough therapy designation in this setting. The agency noted that patients should stop treatment if they develop symptoms of interstitial lung disease and should entirely go off treatment if lung disease is confirmed. The drug may also cause defects that can lead to heart failure.