The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended the approval of osimertinib (Tagrisso) for the treatment of adult patients with locally advanced, unresectable non-small cell lung cancer (NSCLC) whose tumors have EGFR exon 19 deletions or exon 21 L858R substitution mutations and whose disease has not progressed during or following platinum-based chemoradiation therapy. This decision follows the FDA approval of osimertinib for the same indication in September 2024.
The positive opinion was based on data from the phase 3 LAURA trial (NCT03521154), a double-blind, placebo-controlled study. The trial enrolled patients at least 18 years of age (20 in Japan) with locally advanced, unresectable, stage III NSCLC harboring an EGFR exon 19 deletion or L858R mutation without disease progression following definitive chemoradiotherapy. Patients were randomized 2:1 to receive 80 mg of oral osimertinib or placebo once daily until disease progression, unacceptable toxicity, or other discontinuation criteria were met.
Efficacy of Osimertinib
Treatment with osimertinib (n = 143) led to an 84% reduction in the risk of disease progression or death vs placebo (n = 73; HR, 0.16; 95% CI, 0.10-0.24; P < .001). Median progression-free survival (PFS) as assessed by blinded independent central review (BICR) was 39.1 months (95% CI, 31.5-not calculable) with osimertinib vs 5.6 months (95% CI, 3.7-7.4) with placebo. The 12- and 24-month PFS rates in the osimertinib arm were 74% and 65%, respectively, compared to 22% and 13% in the placebo arm. Overall survival (OS) data were immature at the time of the last analysis, and follow-up is ongoing to assess OS as a secondary end point; however, despite 81% of patients crossing over to receive osimertinib from the placebo arm, an OS trend favoring osimertinib was noted (HR, 0.81; 95% CI, 0.42-1.56; P = .530).
Objective response rate was 57% (95% CI, 49%-66%) with osimertinib vs 33% (95% CI, 22%-45%) with placebo. The disease control rates were 89% (95% CI, 83%-94%) and 79% (95% CI, 68%-88%) with osimertinib and placebo, respectively. The median duration of response was also prolonged with osimertinib, at 36.9 months (95% CI, 30.1-NC) vs 6.5 months (95% CI, 3.6-8.3) with placebo.
Safety Profile
Regarding safety, the most common any-grade adverse effects (AEs) that occurred in at least 10% of patients included radiation pneumonitis (osimertinib, 48%; placebo, 38%), diarrhea (36%; 14%), rash (24%; 14%), COVID-19 (20%; 8%), paronychia (17%; 1%), cough (16%; 10%), decreased appetite (15%; 5%), dry skin (13%; 5%), pruritus (13%; 7%), stomatitis (12%; 3%), decreased white blood cell count (12%; 3%), pneumonia (11%; 8%), anemia (10%; 4%), and musculoskeletal chest pain (3%; 12%). Grade 3 or higher AEs in the osimertinib arm included pneumonia (3%), radiation pneumonitis (2%), diarrhea (2%), COVID-19 (1%), decreased appetite (1%), dry skin (1%), decreased white blood cell count (1%), and anemia (1%).
Expert Commentary
"The LAURA results build on the established efficacy of osimertinib and support the approval of the first targeted therapy for patients with unresectable, EGFR-mutated lung cancer," said Manuel Cobo, MD, specialist physician of the Medical Oncology Service at the Carlos Haya University Hospital in Malaga, Spain. Susan Galbraith, executive vice president, Oncology R&D, AstraZeneca, added, "[This] news reinforces [osimertinib] as the backbone therapy in EGFR-mutated NSCLC, meeting the critical unmet need for an effective targeted treatment option in the unresectable setting."
