What FDA Approvals Cover Tagrisso for NSCLC?
Tagrisso (osimertinib) is approved for first-line treatment of metastatic non-small cell lung cancer (NSCLC) with exon 19 deletions or exon 21 L858R mutations in EGFR, detected by an FDA-approved test.[1]
It is also approved for adjuvant therapy after tumor resection in patients with NSCLC harboring the same EGFR mutations (exon 19 deletions or exon 21 L858R), with no evidence of stage IV disease.[1]
Additional approval exists for treatment of locally advanced or metastatic NSCLC with EGFR T790M mutation, detected by an FDA-approved test, in patients whose disease progressed on or after EGFR tyrosine kinase inhibitor (TKI) therapy.[1]
How Do Patients Get Tested for These Mutations?
EGFR mutation status is confirmed via tumor biopsy or plasma (liquid biopsy). FDA-approved companion diagnostics include cobas EGFR Mutation Test v2 and therascreen EGFR Plasma RGQ PCR Kit. Testing occurs before starting Tagrisso to match the specific mutation.[1]
What Stages of NSCLC Does Tagrisso Target?
Primarily metastatic (stage IV) or locally advanced NSCLC, and early-stage (IB-IIIA) as adjuvant post-surgery. It does not have approvals for frontline use in EGFR wild-type NSCLC or other mutation subtypes like exon 20 insertions without prior TKI failure.[1]
When Was Tagrisso First Approved for NSCLC and What Expanded It?
Initial FDA approval came in 2015 for T790M-mutated metastatic NSCLC post-EGFR TKI progression. Expanded in 2018 to first-line metastatic EGFR-mutated NSCLC based on FLAURA trial data showing improved progression-free and overall survival. Adjuvant approval followed in 2020 from ADAURA trial.[1][2]
How Does Tagrisso Compare to Other EGFR TKIs in NSCLC?
Tagrisso, a third-generation irreversible EGFR TKI, outperforms first-generation (erlotinib, gefitinib) and second-generation (afatinib, dacomitinib) TKIs in first-line settings per FLAURA trial: median progression-free survival of 18.9 months vs. 10.2 months for first-gen TKIs.[2] It crosses the blood-brain barrier better, addressing CNS metastases common in EGFR-mutated NSCLC.[1]
What Limitations or Exclusions Apply?
Not indicated for NSCLC without EGFR mutations. Use requires confirmed mutation status. No approval as monotherapy in frontline for non-EGFR mutated disease or combination frontline without specific trial data.[1]
[1]: FDA Label for Tagrisso
[2]: NEJM: FLAURA Trial