Mustafa Özgüroğlu, Myung-Ju Ahn, Xiaorong Dong, James Chih-Hsin Yang, Satoshi Oizumi, Koichi Goto, Manuel Cobo, Sang-We Kim, Te-Chun Hsia, Jarin Chindaprasirt, Fernanda Fujiki, Natalia Valdiviezo, Ignacio Casarini, Terufumi Kato, Xiangning Huang, Azura Evans, Elena Armenteros-Monterroso, Ana Bolanos, Suresh S Ramalingam, Shun Lu
Osimertinib demonstrated clinically meaningful improvements versus placebo in TFST, PFS2 and TSST, and a trend towards OS benefit. These data indicate that clinical benefit with osimertinib was preserved beyond first progression, supporting long-term benefits of osimertinib for unresectable stage III EGFR-mutated NSCLC without progression during/after definitive chemoradiotherapy.
INTRODUCTION: In the phase III LAURA study, osimertinib demonstrated statistically significant improvement in progression-free survival (PFS) versus placebo in patients with unresectable stage III EGFR-mutated non-small cell lung cancer (NSCLC) without disease progression during/after chemoradiotherapy. We report pre-specified post-progression outcomes, subsequent treatments and a second interim analysis of overall survival (OS).
METHODS: Patients were randomized 2:1 to receive osimertinib or placebo until progression (blinded independent central review) or discontinuation. Open-label osimertinib was offered post-progression. Secondary endpoints included time to first and second subsequent treatment (TFST and TSST), second PFS (PFS2) and OS.
RESULTS: At primary data cutoff (January 5, 2024), TFST (hazard ratio [HR], 0.13; 95% CI, 0.08-0.21), PFS2 (0.62; 0.35-1.08) and TSST (0.51; 0.28-0.91) were improved with osimertinib versus placebo. As reported previously, 63/143 (44%) and 66/73 (90%) patients had discontinued randomized osimertinib and placebo treatment, respectively. The most common first subsequent systemic treatment was an EGFR-tyrosine kinase inhibitor in the osimertinib and placebo arms (22/63 [35%] and 56/66 [85%], respectively), primarily osimertinib (14/63 [22%] and 50/66 [76%]). At the second interim OS analysis (data cutoff: November 29, 2024), there was a trend towards OS benefit with osimertinib versus placebo (HR, 0.67; 95% CI, 0.40-1.14; 31% maturity).
CONCLUSIONS: Osimertinib demonstrated clinically meaningful improvements versus placebo in TFST, PFS2 and TSST, and a trend towards OS benefit. These data indicate that clinical benefit with osimertinib was preserved beyond first progression, supporting long-term benefits of osimertinib for unresectable stage III EGFR-mutated NSCLC without progression during/after definitive chemoradiotherapy.