On April 18, 2018, the FDA expanded approval to AstraZeneca Pharmaceuticals Inc. to market TAGRISSO® (osimertinib) for the treatment of frontline epidermal growth factor receptor (EGFR)-mutant-positive non-small cell lung cancer (NSCLC) . EGFR is a tyrosine kinase receptor that can activate cellular growth and survival pathways and activating mutations in the EGFR gene have been identified in approximately 15-50% of NSCLC adenocarcinoma samples . The most common EGFR alterations found in NSCLC samples include deletions in exon 19 and a single base substitution in exon 21, L858R, which are both sensitive to first- and second-generation tyrosine kinase inhibitors (TKIs) erlotinib (TARCEVA®), gefitinib (IRESSA®), and afatinib (GIOTRIF®) . Unfortunately, almost all patients develop resistance to these therapies within two years, and thus there is a need for therapies that provide durable remissions in patients with EGFR-mutant-positive NSCLC . Osimertinib is a third generation TKI that inhibits common EGFR mutants such as exon 19 deletions and L858R, as well as the TKI-resistant mutant T790M . It was initially approved in 2015 for the treatment of patients with EGFR T790M mutation-positive NSCLC .
The expanded approval was based on the results of a randomized phase 3 trial, FLAURA, assessing the safety and efficacy of osimertinib vs. gefitinib or erlotinib in the frontline treatment of EGFR-mutant (exon 19 or L858R) NSCLC (NCT02296125) . Patients in the osimertinib arm experienced a longer progression-free survival than those in the gefitinib/erlotinib arm, 18.9 months vs. 10.2 months, respectively . Additionally, the median duration of response experienced by patients receiving osimertinib was longer at 17.2 months vs. patients receiving standard TKIs, 8.5 months . These results suggest that osimertinib can produce durable responses for frontline patients with EGFR-mutant NSCLC.
- TAGRISSO® (osimertinib) tablets, for oral use ClinicalTrials.gov 04/18/2018 [cited 2018 May 4]; Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/208065s008lbl.pdf.
- Zhang, Y.L., et al., The prevalence of EGFR mutation in patients with non-small cell lung cancer: a systematic review and meta-analysis. Oncotarget, 2016. 7(48): p. 78985-78993.
- Heydt, C., et al., Novel approaches against epidermal growth factor receptor tyrosine kinase inhibitor resistance. Oncotarget, 2018. 9(20): p. 15418-15434.
- Soria, J.C., et al., Osimertinib in Untreated EGFR-Mutated Advanced Non-Small-Cell Lung Cancer. N Engl J Med, 2018. 378(2): p. 113-125.
- TAGRISSO™ (osimertinib) tablet, for oral use. Initial U.S. Approval: 2015. Drugs@FDA: FDA Approved Drug Products [cited 2018 May 4 ]; Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/208065s000lbl.pdf.
- AZD9291 Versus Gefitinib or Erlotinib in Patients With Locally Advanced or Metastatic Non-small Cell Lung Cancer (FLAURA). ClinicalTrials.gov [cited 2018 May 4]; Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/208065s008lbl.pdf.