The FDA has approved osimertinib (Tagrisso®, AstraZeneca) for patients with surgically resected early-stage non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 L858R mutations. Previously approved for the first-line treatment of metastatic EGFR-mutated disease, osimertinib is the first adjuvant therapy to be approved for patients with EGFR-mutated NSCLC.
The approval was based on the phase 3 ADAURA trial (NCT02511106). "Approximately 30% of patients with NSCLC present with early stage (I-IIIA) disease; surgery is the primary treatment," wrote the study's investigators, led by Roy S. Herbst, MD, PhD, Chief of Medical Oncology at Yale Cancer Center, in the abstract from their presentation at the American Society of Clinical Oncology (ASCO) Virtual Scientific Program in June 2020. "Adjuvant chemotherapy is standard of care in patients with resected stage II-III NSCLC and select stage IB patients; however, recurrence rates are high, and other therapies are needed."
The trial enrolled 682 patients with stage IB/II/IIIA nonsquamous NSCLC with EGFR exon 19 deletions or exon 21 L858R mutations, all of whom had undergone complete tumor resection. Patients were randomized in a 1:1 ratio to receive 80 mg osimertinib once daily or placebo for up to three years. The primary end point was disease-free survival in patients with stage II–IIIA disease, with secondary end points of overall survival and safety.
In patients with stage II–IIIA disease, osimertinib produced a significantly higher two-year disease-free survival rate compared with placebo (90% vs 44%), with a hazard ratio of 0.17. The two-year disease-free survival rate was also improved with osimertinib in the overall study population (89% vs 53%), with a hazard ratio of 0.21. At data cutoff, overall survival data were immature, with 9 deaths in the osimertinib group and 20 deaths in the placebo group. Safety data were consistent with the known safety profile for osimertinib.
The most common adverse events occurring in at least 20% of patients receiving osimertinib are leukopenia, lymphopenia, thrombocytopenia, diarrhea, anemia, rash, musculoskeletal pain, nail toxicity, neutropenia, dry skin, stomatitis, fatigue, and cough. Serious adverse events were experienced by 16% of patients. The prescribing information for osimertinib contains a warning that interstitial lung disease/pneumonitis, QTc interval prolongation, cardiomyopathy, keratitis, erythema multiforme and Stevens-Johnson syndrome, cutaneous vasculitis, and embryo-fetal toxicity may occur.
"Adjuvant osimertinib is the first targeted agent in a global trial to show a statistically significant and clinically meaningful improvement in disease-free survival in patients with stage IB/II/IIIA EGFR-mutated NSCLC after complete tumor resection and adjuvant chemotherapy when indicated," concluded Dr. Herbst and colleagues. "Adjuvant osimertinib provides an effective new treatment strategy for these patients."
The recommended dose of osimertinib is 80 mg taken orally once daily, with or without food, for up to three years or until disease recurrence.
For More Information
Herbst RS, Tsuboi M, John T, et al (2020). Osimertinib as adjuvant therapy in patients (pts) with stage IB-IIIA EGFR mutation positive (EGFRm) NSCLC after complete tumor resection: ADAURA. J Clin Oncol (ASCO Virtual Scientific Program Abstracts), 38(suppl_18). Abstract LBA5. DOI:10.1200/JCO.2020.38.18_suppl.LBA5
Clinicaltrials.gov (2020). AZD9291 versus placebo in patients with stage IB-IIIA non-small cell lung carcinoma, following complete tumour resection with or without adjuvant chemotherapy (ADAURA). NLM identifier: NCT02511106.
US Food & Drug Administration (2020). FDA approves first adjuvant therapy for most common type of lung cancer. Available at: https://www.fda.gov/news-events/press-announcements/fda-approves-first-adjuvant-therapy-most-common-type-lung-cancer
Image credit: Ventana Medical Systems, Inc. Licensed under CC BY-SA 4.0