During a planned interim safety analysis and futility review (February 2019), the independent data monitoring committee (IDMC) requested key efficacy data to review at the next planned meeting (April 2020). Efficacy ResultsĪ total of 682 patients in ADAURA were randomized to receive either osimertinib 80 mg daily or placebo for up to 3 years or until disease recurrence or toxicity. After baseline brain imaging, subsequent scans were obtained as clinically indicated according to the investigator's discretion. Follow-up CT scans for tumor assessment were performed at 12 and 24 weeks, then every 24 weeks for 5 years and once yearly thereafter. Secondary endpoints were OS, safety, and tolerability. The primary efficacy outcome measure was DFS per investigator assessment. Patients were randomized 1:1 to osimertinib 80 mg daily or placebo for up to 3 years, and randomization was stratified by stage (IB vs. Patients could have received adjuvant platinum-based chemotherapy (≤4 cycles). Patients were not permitted to have received pre- or postoperative radiation therapy or EGFR TKI. Complete surgical resection with negative margins for tumor was required, and baseline brain imaging with either MRI or CT was performed prior to randomization. ![]() Patients had confirmed EGFR Ex19del or L858R mutations the presence of other coexisting EGFR mutations was permitted. The approval of osimertinib as adjuvant therapy was based on the ADAURA study, a double-blind, randomized, placebo-controlled trial in patients with primarily nonsquamous NSCLC classified postoperatively as stage IB to IIIA according to the American Joint Committee on Cancer (AJCC) 7th edition TNM staging system. ![]() In a pooled analysis by the Lung Adjuvant Cisplatin Evaluation collaborative group, the HR for overall survival (OS) in patients with early-stage NSCLC who were treated with adjuvant chemotherapy versus no chemotherapy after resection was 0.89 (95% CI, 0.82–0.96), corresponding to a 5-year absolute benefit of 5.4% from chemotherapy the HR for disease-free survival (DFS) was 0.84 (95% CI, 0.78–0.91 ref. However, disease recurrence or death following surgery and adjuvant chemotherapy is high across all disease stages, with 5-year survival rates ranging from 39% for stage IIIA to 67% for stage IB disease ( 5). Although surgery is the primary treatment for patients with early-stage NSCLC, adjuvant platinum-based chemotherapy is recommended for patients with resected stage II to IIIA disease and a select group of patients with stage IB disease with high-risk features. 3) and only 30% of patients present with resectable disease at the time of diagnosis ( 4). In the United States, approximately 80% to 85% of lung cancer is non–small cell lung cancer (NSCLC ref. This is the first targeted therapy adjuvant approval for NSCLC and has practice-changing implications.ĭespite reports of decreasing mortality with advances in treatment, lung cancer remains the leading cause of cancer deaths worldwide ( 1, 2). This application was reviewed under FDA's Project Orbis, in collaboration with Australia Therapeutic Goods Administration, Brazil ANVISA, Health Canada, Singapore Health Sciences Authority, Switzerland Swissmedic, and the United Kingdom Medicines and Healthcare products Regulatory Agency. Overall survival data were not mature at the time of the approval. Median DFS was not reached for the osimertinib arm compared with 27.5 months (95% CI, 22.0–35.0) for patients receiving placebo. Disease-free survival (DFS) in the overall population (stage IB–IIIA) was improved for patients who received osimertinib, with an HR of 0.20 95% confidence interval (CI), 0.15–0.27 P < 0.0001. ![]() The approval was based on the ADAURA study, in which 682 patients with NSCLC were randomized to receive osimertinib ( n = 339) or placebo ( n = 343). On December 18, 2020, the FDA approved osimertinib as adjuvant therapy in patients with non–small cell lung cancer (NSCLC) whose tumors have EGFR exon 19 deletions or exon 21 (L858R) mutations, as detected by an FDA-approved test.
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