The Food and Drug Administration (FDA) has approved Tagrisso® (osimertinib; AstraZeneca) as adjuvant therapy after tumor resection in patients with non-small cell lung cancer (NSCLC) whose tumors have epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 L858R mutations, as detected by an FDA-approved test.

The approval was based on data from the double-blind, placebo-controlled phase 3 ADAURA study, which assessed the efficacy and safety of osimertinib in 682 adults with EGFR exon 19 deletions or exon 21 L858R mutation-positive NSCLC who had complete tumor resection, with or without prior adjuvant chemotherapy. Patients were randomized 1:1 to receive osimertinib 80mg orally once daily (n=339) or placebo (n=343) following recovery from surgery and standard adjuvant chemotherapy, if given.

The primary end point was disease-free survival (DFS) in patients with stage II to IIIA NSCLC, defined as reduction in the risk of disease recurrence or death. The key secondary end points included DFS in the overall population (stage IB to IIIA NSCLC), and overall survival (OS) in patients with stage II to IIIA NSCLC and in the overall population.

Findings showed that treatment with osimertinib resulted in a statistically significant and clinically meaningful 83% reduction in the risk of disease recurrence or death in the primary analysis population (hazard ratio [HR] 0.17; 95% CI, 0.12-0.23; P <.0001). The median DFS was not reached (95% CI, 38.8-not estimable [NE]) in the osimertinib treatment arm and was 19.6 months (95% CI, 16.6-24.5) in the placebo arm. 


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In the overall study population, osimertinib reduced the risk of disease recurrence or death by 80% (HR 0.20; 95% CI, 0.15-0.27; P <.0001). The median DFS was not reached (95% CI, NE-NE) in the osimertinib arm and was 27.5 months (95% CI, 22.0-35.0) in the placebo arm. At the time of DFS analysis, OS data were not mature with 27% of the 94 deaths required for the final analysis of OS in patients with stage II to IIIA disease.

“Adjuvant Tagrisso has demonstrated an unprecedented disease-free survival benefit for early-stage lung cancer patients with EGFR mutations who face high rates of recurrence even after successful surgery and subsequent chemotherapy,” said Roy S. Herbst, MD, PhD, chief of Medical Oncology at Yale Cancer Center and Smilow Cancer Hospital, New Haven, CT and principal investigator in the ADAURA phase 3 trial. “This approval reinforces how critical it is to test all lung cancer patients for EGFR mutations before deciding how to treat them and regardless of their stage at diagnosis.”

Tagrisso, a kinase inhibitor, is already indicated for the first-line treatment of patients with metastatic NSCLC whose tumors have EGFR exon 19 deletions or exon 21 L858R mutations, as detected by an FDA-approved test. It is also approved for the treatment of patients with metastatic EGFR T790M mutation-positive NSCLC, as detected by an FDA-approved test, who have progressed on or after EGFR tyrosine kinase inhibitor therapy.

For more information visit astrazeneca-us.com.

References

  1. FDA approves osimertinib as adjuvant therapy for non-small cell lung cancer with EGFR mutations. [press release]. Silver Springs, MD: U.S. Food & Drug Administration; December 18, 2020. 
  2. Tagrisso approved in the US for the adjuvant treatment of patients with early-stage EGFR-mutated lung cancer. Wilmington, DE: AstraZeneca; December 21, 2020.
  3. Tagrisso [package insert]. Wilmington, DE: AstraZeneca; 2020.