On December 18, 2020, the FDA approved osimertinib (Tagrisso; AstraZeneca) for adjuvant therapy after tumor resection in patients with non–small-cell lung cancer (NSCLC) and EGFR exon 19 deletions or exon 21 L858R mutations, as detected by an FDA-approved test. The FDA approved this application 2 months ahead of the FDA goal date and granted it a breakthrough therapy designation.
Osimertinib was previously approved for the first-line treatment of metastatic NSCLC and EGFR exon 19 deletions or exon 21 L858R mutations, and for the treatment of metastatic NSCLC and EGFR T790M mutation after EGFR tyrosine kinase inhibitor therapy.
The FDA approved the new indication based on a randomized, double-blind, placebo-controlled clinical trial in 682 patients with NSCLC and EGFR exon 19 deletions or exon 21 L858R mutation who had complete tumor resection, with or without previous adjuvant chemotherapy. Eligible patients with resectable (stage II-IIIA) tumors had to have predominantly nonsquamous histology and EGFR exon 19 deletions or exon 21 L858R mutations.
The patients were randomized in a 1:1 ratio to oral osimertinib 80 mg once daily or to placebo after recovery from surgery and standard adjuvant chemotherapy, if used.
The major efficacy outcome measure was disease-free survival (DFS) in patients with stage II to stage IIIA NSCLC. The median DFS was not reached in the osimertinib arm compared with 19.6 months in the placebo arm (hazard ratio [HR], 0.17; 95% confidence interval [CI], 0.12-0.23; P <.0001). The secondary efficacy end point was DFS in the overall study population; the median was not reached in the osimertinib arm versus 27.5 months in the placebo arm (HR, 0.20; 95% CI, 0.15-0.27; P <.0001).
The most common (>20%) adverse reactions reported with osimertinib, including laboratory abnormalities, were lymphopenia, leukopenia, thrombocytopenia, diarrhea, anemia, rash, musculoskeletal pain, nail toxicity, neutropenia, dry skin, stomatitis, fatigue, and cough.
The recommended dose of osimertinib as adjuvant treatment of early-stage NSCLC is 80 mg once daily until disease recurrence or until unacceptable adverse events, or for up to 3 years.