On December 18, 2020, the U.S. Food and Drug Administration (FDA) approved osimertinib (Tagrisso®) as adjuvant therapy after tumor resection for 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. 

Efficacy was demonstrated in a randomized, double-blind, placebo-controlled trial (ADAURA; NCT02511106) in patients with EGFR exon 19 deletions or L858R mutation-positive NSCLC who had 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 L858R mutations identified prospectively from tumor tissue in a central laboratory by the cobas® EGFR Mutation Test. A total of 682 patients were randomized one to one to receive osimertinib 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 (DFS) in patients with stage II–IIIA NSCLC determined by investigator assessment. Median DFS was not reached (38.8, not evaluated) in patients in the osimertinib arm compared to 19.6 months (16.6, 24.5) in the placebo arm (hazard ratio [HR] = 0.17 95% CI = 0.12, 0.23; p < 0.0001). DFS in the overall study population was a secondary efficacy outcome measure; the median was not reached (not evaluated, not evaluated) in patients in the osimertinib arm compared to 27.5 months (22, 36) in those in the placebo arm (HR = 0.20 95% CI = 0.15, 0.27; p < 0.0001). 

The recommended osimertinib dose for adjuvant treatment of early-stage NSCLC is 80 mg orally once daily, with or without food, until patients experience disease recurrence or unacceptable toxicity, or for up to three years. 

Most common adverse reactions (> 20%) 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. 

View the full prescribing information for osimertinib. 

The review was conducted under Project Orbis, an initiative of FDA’s Oncology Center of Excellence. Project Orbis provides a framework for concurrent submission and review of oncology drugs among international partners. For the review, FDA collaborated with the Australian Therapeutic Goods Administration, Brazilian Health Regulatory Agency, Health Canada, Singapore’s Health Sciences Authority, and Switzerland’s Swissmedic. The application reviews are ongoing at the other regulatory agencies. 

The review used the Real Time Oncology Review pilot program, which streamlined data submission prior to filing the entire clinical application, and Assessment Aid, a voluntary submission from the applicant to facilitate FDA’s assessment. FDA approved the application two months ahead of its goal date. 

The application was granted breakthrough designation. A description of FDA expedited programs is in the Guidance for Industry—Expedited Programs for Serious Conditions—Drugs and Biologics.   

Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System or by calling 800-FDA-1088.         

For assistance with single-patient oncology investigational new drug applications, contact OCE’s Project Facilitate at 240-402-0004 or email OncProjectFacilitate@fda.hhs.gov.