Dr Haggstrom on the Role of Osimertinib in Unresectable EGFR-Mutated NSCLC

Daniel E. Haggstrom, MD, Hematology, Medical Oncology (Cancer), Atrium Health Levine Cancer Institute, discusses the role of osimertinib (Tagrisso) in the treatment of unresectable EGFR-mutated non-small cell lung cancer (NSCLC) following the phase 3 LAURA trial (NCT03521154).

Notably, in September of 2024, the FDA approved treatment with osimertinib for adult patients with locally advanced, unresectable, stage III NSCLC. These were patients whose disease has not progressed during or following concurrent or sequential platinum-based chemoradiation therapy and whose tumors have EGFR exon 19 deletions or exon 21 L858R mutations, as detected by an FDA-approved test. Furthermore, this regulatory decision was supported by data from the LAURA.

The LAURA trial represents the first successful integration of targeted therapy into the stage III space for EGFR-mutated NSCLC, Haggstrom begins. Patients who completed chemoradiation therapy and achieved a confirmed response were randomized to receive either osimertinib, an EGFR TKI, or placebo. Progression-free survival (PFS) served as the primary end point of the investigation. Data that led to the regulatory approval showed that patients treated with osimertinib (n = 143) had a median PFS of 39.1 months (95% CI, 31.5–not estimable) compared with 5.6 months (95% CI, 3.7-7.4) in the placebo group (n = 73; HR, 0.16; 95% CI, 0.10-0.24; P < .001). This improvement underscores osimertinib’s efficacy in controlling NSCLC in this patient population, Haggstrom emphasizes.

The trial also indicated a potential trend toward improved overall survival (OS) with osimertinib, though OS data remain immature due to a high crossover rate from placebo to active treatment, Haggstrom continues. The therapy's manageable toxicity and PFS benefits led to a shift in the standard of care for this patient population, Haggstrom explained. Safety and tolerability of osimertinib were consistent with its known profile, with toxicity levels manageable even in patients who had undergone intensive chemoradiation therapy.

The LAURA trial underscores the evolving role of targeted therapy in earlier-stage NSCLC and its potential to improve outcomes where immunotherapy may be less effective, Haggstrom concludes.