On 25 September 2024, the US Food and Drug Administration (FDA) approved osimertinib (Tagrisso, AstraZeneca Pharmaceuticals) for adult patients with locally advanced, unresectable (stage III) non-small cell lung cancer (NSCLC) whose disease has not progressed during or following concurrent or sequential platinum-based chemoradiation therapy and whose tumours have EGFR Exon 19 deletions or Exon 21 L858R mutations, as detected by an FDA-approved test.
Efficacy was evaluated in LAURA (NCT03521154), a double blind, randomised, placebo-controlled study in 216 adult patients with locally advanced, unresectable stage III NSCLC with EGFR Exon 19 deletions or Exon 21 L858R mutations who had not progressed during or following definitive platinum-based chemoradiation within 42 days prior to study randomisation. Patients were randomised (2:1) to receive either osimertinib 80 mg orally once daily or placebo until disease progression or unacceptable toxicity.
The major efficacy outcome measure was progression-free survival (PFS) as assessed by blinded independent central review. Additional efficacy outcome measures included overall survival (OS). Osimertinib demonstrated a statistically significant improvement in PFS compared to placebo with a hazard ratio of 0.16 (95% confidence interval [CI] 0.10, 0.24; p-value < 0.001). The median PFS was 39.1 months (95% CI 31.5, not estimable) in the osimertinib arm and 5.6 months (95% CI 3.7, 7.4) in the placebo arm.
While OS results were immature at the current analysis, with 36% of pre-specified deaths for the final analysis reported, no trend towards a detriment was observed.
The most common adverse reactions, including laboratory abnormalities (≥20%), were lymphopenia, leukopenia, interstitial lung disease/pneumonitis, thrombocytopenia, neutropenia, rash, diarrhoea, nail toxicity, musculoskeletal pain, cough, and COVID-19 infection.
The recommended osimertinib dose is 80 mg once daily, with or without food, until disease progression or unacceptable toxicity.
This review was conducted under Project Orbis, an initiative of the FDA’s Oncology Center of Excellence (OCE). Project Orbis provides a framework for concurrent submission and review of oncology drugs among international partners. For this review, FDA collaborated with the Australian Therapeutic Goods Administration, Health Canada, and Swissmedic. The application reviews are ongoing at the other regulatory agencies.
This review used the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment.
This application was granted priority review and breakthrough designation.
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.
For assistance with single-patient INDs for investigational oncology products, healthcare professionals may contact OCE’s Project Facilitate.