On December 18, the U.S. Food and Drug Administration (FDA) approved osimertinib (Tagrisso) for 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.
ADAURA
Efficacy was demonstrated in the randomized, double-blind, placebo-controlled ADAURA trial. The study included patients with NSCLC and EGFR exon 19 deletions or exon 21 L858R mutations who had undergone a complete tumor resection, with or without prior adjuvant chemotherapy.
Eligible patients with resectable tumors (stage IB–IIIA) were required to have predominantly nonsquamous histology and EGFR exon 19 deletions or exon 21 L858R mutations identified prospectively from tumor tissue in a central laboratory by the cobas EGFR Mutation Test. A total of 682 patients were randomly assigned 1:1 to receive osimertinib at 80 mg orally once daily or placebo following recovery from surgery and standard adjuvant chemotherapy, if given.
The major efficacy outcome measure was disease-free survival in patients with stage II–IIIA NSCLC determined by investigator assessment. Median disease-free survival was not reached (range = 38.8 months–not evaluable) in patients treated with osimertinib compared with 19.6 months (range = 16.6–24.5 months) in patients treated with placebo (hazard ratio [HR] = 0.17, 95% confidence interval [CI] = 0.12–0.23, P < .0001). Disease-free survival in the overall study population was a secondary efficacy outcome measure; the median was not reached (range = not evaluable–not evaluable) in patients in the osimertinib arm compared with 27.5 months (range = 22–36 months) in the placebo arm (HR = 0.20, 95% CI = 0.15–0.27, P < .0001).
The most commonly reported (> 20%) adverse reactions in patients taking osimertinib, including laboratory abnormalities, were lymphopenia, leukopenia, thrombocytopenia, diarrhea, anemia, rash, musculoskeletal pain, nail toxicity, neutropenia, dry skin, stomatitis, fatigue, and cough.
The recommended osimertinib dose for adjuvant treatment of early-stage NSCLC is 80 mg orally once daily, with or without food, until disease recurrence, unacceptable toxicity, or for up to 3 years.
