December 18, 2020 - The FDA has approved osimertinib for use as an adjuvant treatment following tumor resection in patients with non–small cell lung cancer whose tumors harbor EGFR exon 19 deletions or exon 21 L858R mutations, as detected by an FDA-approved test.
The FDA has approved osimertinib (Tagrisso) for use as an adjuvant treatment following tumor resection in patients with non–small cell lung cancer whose tumors harbor EGFR exon 19 deletions or exon 21 L858R mutations, as detected by an FDA-approved test.1
The regulatory decision was based on data from the double-blind, placebo-controlled, phase 3 ADAURA trial (NCT02511106), which showed that osimertinib, when used as an adjuvant therapy, led to a statistically significant improvement in disease-free survival (DFS) in patients with stage IB/II/IIIA EGFR-mutated NSCLC. Per investigator assessment, the median DFS had not yet been reached in patients who received osimertinib vs 19.6 months in those who received placebo (HR, 0.17; 95% CI, 0.12-0.23; P <.0001).
In the overall study population, the median DFS was not yet reached vs 27.5 months in the investigative and control arms, respectively (HR, 0.20; 95% CI, 0.15-0.27; P <.0001).
A total of 682 patients with NSCLC that harbored EGFR exon 19 deletions or exon 21 L858R mutations, who had complete tumor resection, with or without previous adjuvant chemotherapy were enrolled to the trial. To be eligible for enrollment, they needed to have resectable tumors, stage IB-IIIA, predominant nonsquamous histology, and the aforementioned mutations, which were prospectively detected from tumor tissue via the cobas EGFR Mutation Test in a central laboratory.
Participants were randomized 1:1 to receive either oral osimertinib at a once-daily dose of 80 mg or placebo following recovery from surgery and standard adjuvant chemotherapy, if administered.
The primary objective of the trial is DFS per investigator assessment. Secondary end points comprise DFS in the overall population; DFS at 2, 3, 4, and 5 years; overall survival (OS), safety, and health-related quality of life.
Previous data presented during the 2020 ASCO Virtual Scientific Program showed that the median DFS in the subset of patients with stage II/IIIA disease had not yet been reached with osimertinib arm vs 20.4 months with placebo (HR, 0.17; 95% CI, 0.12-0.23; P <.0001).2
The DFS rates at 2 years in those with stage IB disease were 87% vs 73% (HR, 0.50; 95% CI, 0.25-0.96), respectively, in patients who received osimertinib vs placebo. These rates were 91% vs 56%, respectively, in those with stage II disease (HR, 0.17; 95% CI, 0.08-0.31) and 88% vs 32%, respectively, in those with stage IIIA disease (HR, 0.12; 95% CI, 0.07-0.20).
The OS data are still immature, at just 5% maturity, and the median OS has not yet been reached in either arm (HR, 0.40; 95% CI, 0.18-0.90).
Regarding safety, the most commonly experienced adverse effects in those who received osimertinib included laboratory abnormalities such as lymphopenia, leukopenia, thrombocytopenia, diarrhea, anemia, rash, musculoskeletal pain, nail toxicity, neutropenia, dry skin, stomatitis, fatigue, and cough.