Phase 3 LAURA Trial Plenary Presentation Receives Standing Ovation

Osimertinib following definitive chemoradiotherapy (CRT) showed a statistically significant and “clinically meaningful” improvement in progression-free survival (PFS) for patients with unresectable stage III EGFR-mutated non-small cell lung cancer (NSCLC), according to results from the phase 3 LAURA trial.

The results of the study establish osimertinib as the new standard of care for EGFR-mutated NSCLC in this setting, according to the study authors, led by Suresh S. Ramalingam, MD, FACP, FASCO, of the Winship Cancer Institute at Emory University. Dr. Ramalingam presented primary results from the trial during a plenary session held at the 2024 American Society of Clinical Oncology Annual Meeting.

Osimertinib, a third-generation EGFR-tyrosine kinase inhibitor with activity in the central nervous system, is currently recommended for EGFR-mutated advanced/metastatic NSCLC and as an adjuvant therapy for resectable EGFR-mutated NSCLC, according to the study investigators. However, the “benefit of consolidation immunotherapy specifically for EGFR-[mutated] NSCLC remains uncertain, with limited data available,” Dr. Ramalingam and colleagues explained.

LAURA, a double-blinded and placebo-controlled phase 3 trial, assessed the efficacy and safety of osimertinib in adults with unresectable stage III EGFR-mutated (Ex19del/L858R) NSCLC who received definitive platinum-based concurrent CRT/sequential CRT and did not have progression. The patients had a World Health Organization performance status of 0 or 1.

The investigators randomized 216 patients 2:1 to receive osimertinib 80 mg (n=143) or placebo (n=73) once a day until progression, as confirmed by a blinded independent central review (BICR), or discontinuation. The researchers stratified patients by multiple characteristics, including if they had received concurrent versus sequential CRT, had stage IIIA disease versus stage IIIB/IIIC, and if they were Chinese or not Chinese. The baseline characteristics were “generally balanced” between the study arms, with similar proportions of female patients and stage IIIA, IIIB, IIIC, and Ex19del disease in each arm.

The study mandated imaging, including brain magnetic resonance imaging, at baseline, then every 8 weeks until week 48, and then every 12 weeks until progression per BICR. Patients were offered open-label osimertinib after progression was confirmed. The primary end point of the study was PFS, as assessed by BICR. Secondary end points included overall survival (OS) and safety. The data cutoff was January 5, 2024.

The study showed that osimertinib significantly improved PFS per BICR compared with placebo (hazard ratio [HR], 0.16; P<.001). The median PFS was 39.1 months in patients receiving osimertinib (95% CI, 31.5 to not calculable) and 5.6 months for those receiving placebo (95% CI, 3.7-7.5). The 12-month PFS rate was 74% in patients receiving osimertinib, nearly 3 times higher than the rate of 22% in those receiving placebo. The 24-month PFS rate was 65% in patients receiving osimertinib and 13% in those receiving placebo.

The “PFS benefit was consistent across predefined subgroups,” according to the study investigators. An interim OS analysis, with 20% maturity, has shown a “trend in favor” of osimertinib (HR, 0.81; P=.530). Among the patients receiving placebo, 81% received osimertinib after progression.

All-causality adverse events (AEs) were reported in 98% of patients receiving osimertinib and in 88% receiving placebo. AEs of grade ≥3 occurred in 35% of patients receiving osimertinib and in 12% of those receiving placebo. Serious AEs occurred in 38% and 15%, respectively. Radiation pneumonitis AEs occurred in 48% receiving osimertinib and in 38% receiving placebo, with the majority being grade 1 or 2. Any AEs leading to discontinuation were reported in 13% of those receiving osimertinib and in 5% of those receiving placebo.

“[Osimertinib] after definitive CRT demonstrated a statistically significant and clinically meaningful improvement in PFS for unresectable [stage] III EGFR-[mutated] NSCLC, with no unexpected safety signals,” Dr. Ramalingam and colleagues concluded, noting that the study establishes osimertinib as the new standard of care for EGFR-mutated NSCLC in this setting.

Reference

Ramalingam S, Kato T, Dong X, et al. Osimertinib (osi) after definitive chemoradiotherapy (CRT) in patients (pts) with unresectable stage (stg) III epidermal growth factor receptor-mutated (EGFRm) NSCLC: primary results of the phase 3 LAURA study. Presented at the 2024 American Society of Clinical Oncology Annual Meeting; May 31-June 4, 2024; Chicago, Illinois.