Tagrisso Demonstrates 84% Reduction in Disease Progression Risk for EGFR-Mutated Stage 3 NSCLC
Key Insights
The phase 3 LAURA trial showed Tagrisso (osimertinib) reduced the risk of disease progression or death by 84% compared to placebo in patients with locally advanced, unresectable stage 3 EGFR (search)-mutated NSCLC (search) following chemoradiotherapy.
Patients treated with Tagrisso achieved a median progression-free survival of 39.1 months versus 5.6 months for placebo recipients, representing a seven-fold improvement in disease control.
Based on these results, Tagrisso is expected to become the new standard of care for EGFR (search)-mutated, locally advanced NSCLC (search) patients, marking the first targeted therapy approved for this patient population.
Patients with locally advanced, unresectable stage 3 non-small cell lung cancer (NSCLC (search)) harboring EGFR (search) mutations experienced dramatic improvements in disease control following treatment with Tagrisso (osimertinib) after definitive chemoradiotherapy, according to groundbreaking results from the phase 3 LAURA trial presented at the 2024 ASCO Annual Meeting.
The study demonstrated that Tagrisso reduced the risk of disease progression or death by 84% compared to placebo, with patients achieving a median progression-free survival (PFS) of 39.1 months versus 5.6 months for those receiving placebo. This represents a seven-fold improvement in the time patients lived without their disease worsening.
LAURA Trial Results Transform Treatment Landscape
The LAURA trial enrolled 216 patients with locally advanced, unresectable stage 3 NSCLC (search) harboring EGFR (search) exon 19 deletions or L858R mutations who had not experienced disease progression following definitive chemoradiotherapy. Patients were randomly assigned to receive oral Tagrisso (143 patients) or placebo (73 patients) once daily until disease progression or unacceptable toxicity.
The 12- and 24-month PFS rates in the Tagrisso arm were 74% and 65%, respectively, compared to 22% and 13% in the placebo arm. Notably, 22 patients in the Tagrisso group experienced new tumors compared with 68 patients in the placebo group, with brain metastases being significantly reduced (eight patients versus 29 patients).
"Based on these results, [Tagrisso] will become the new standard of care for patients with [EGFR (search)-mutated], locally advanced NSCLC (search) following definitive chemoradiation. EGFR mutation testing should be conducted for patients with stage 3 disease in order for patients to achieve optimal outcomes," stated lead study author Dr. Suresh S. Ramalingam, executive director of Winship Cancer Institute (search) of Emory University.
Safety Profile Remains Manageable
The safety findings for Tagrisso following chemoradiotherapy were consistent with the known safety profile of the EGFR (search) inhibitor. Most side effects were grade 1/2 (mild/moderate) and did not lead to treatment discontinuation. The most common side effects included radiation pneumonitis (48% versus 38% for placebo), diarrhea (36% versus 14%), and rash (24% versus 14%).
Grade 3 or higher side effects in the Tagrisso arm were infrequent, including pneumonia (3%), radiation pneumonitis (2%), and diarrhea (2%). Dr. Ramalingam noted that the side effects were manageable and most were not serious.
FLAURA2 Shows Promise in Advanced Disease
Complementing the LAURA results, the FLAURA2 Phase III trial demonstrated that Tagrisso combined with chemotherapy provided clinically meaningful benefits in advanced EGFR (search)-mutated NSCLC (search). At 41% data maturity, overall survival interim results showed a favorable trend with the combination therapy (hazard ratio 0.75; 95% confidence interval 0.57-0.97).
The combination also showed consistent benefits across post-progression endpoints, including time to first subsequent treatment (HR 0.73), time to progression on second-line therapy (HR 0.70), and time to second subsequent treatment (HR 0.69).
"The improvement in post-progression outcomes with chemotherapy added to standard-of-care osimertinib is encouraging for patients with advanced EGFR (search)-mutated lung cancer, particularly the encouraging trend toward overall survival," said Dr. Pasi A. Jänne, medical oncologist at Dana-Farber Cancer Institute and principal investigator for the FLAURA2 trial.
Addressing Critical Unmet Need
The LAURA trial results are particularly significant as no targeted therapies are currently approved for patients with EGFR (search)-mutated, unresectable, stage 3 NSCLC (search). Dr. David R. Spigel, chief scientific officer of Sarah Cannon Research Institute (search), emphasized that "the LAURA trial is the first to define the role of EGFR-directed therapy in unresectable stage 3 disease" and that "these data have major implications for both patients and oncologists and will change the standard of care for patients with EGFR mutations."
The findings establish Tagrisso as a transformative treatment option for a patient population with limited therapeutic alternatives, potentially reshaping clinical practice guidelines for locally advanced EGFR (search)-mutated NSCLC (search) management.