Osimertinib significantly improves PFS in patients with unresectable stage III EGFR-mutated NSCLC

In the phase 3 LAURA trial, osimertinib treatment in patients with unresectable stage III EGFR-mutated non-small cell lung cancer (NSCLC) after definitive chemoradiotherapy strongly improved progression-free survival (PFS).

In unresectable stage III NSCLC, following chemoradiotherapy without progression, consolidation therapy with durvalumab is the standard-of-care [1]. However, the benefit of consolidation with durvalumab is uncertain in patients with EGRF-mutated NSCLC [2].

Based on real-world data and the results of a phase 2 study, the phase 3 LAURA trial (NCT03521154) evaluated the efficacy and safety of the EGFR tyrosine kinase inhibitor osimertinib in patients with unresectable stage III EGFR-mutated NSCLC with no progression during or following definitive chemoradiotherapy.

A total of 216 participants were 2:1 randomised to receive osimertinib (80 mg daily) until disease progression or toxicity, or a placebo. Participants receiving placebo were allowed to switch to osimertinib after progression. The primary outcome measurement was PFS. Prof. Suresh Ramalingam (Emory School of Medicine, GA, USA) presented the primary results [3].

Osimertinib demonstrated a statistically significant and clinically meaningful improvement in PFS. The median PFS in participants treated with osimertinib was 39.1 months, versus 5.6 months in those treated with placebo (HR 0.16; 95% CI 0.10–0.24; P<0.001; see Figure). The 24-month PFS rates in both arms were 65% and 13%, respectively. The PFS benefit of osimertinib was observed in all defined key subgroups (i.e. sex, age, stage, EGFR mutation status, response to prior chemoradiotherapy).

Figure: Progression-free survival in LAURA [3]



The objective response rate was also improved by osimertinib (57% vs 33%), as was median duration of response (36.9 vs 6.5 months). Participants treated with osimertinib were less likely to develop new lesions (22% vs 68%), particularly in the brain (8% vs 29%). Overall survival data are not yet mature. In the placebo arm, 81% of participants crossed over to osimertinib after confirmed progression.

Based on these primary results, Prof. Ramalingam expected “osimertinib to become the new standard-of-care for patients with unresectable stage III EGFR-mutated NSCLC who have not progressed after definitive chemoradiotherapy.”

1. Spigel DR, et al. J Clin Oncol. 2022; 40: 1301-1311.
2. Naidoo J, et al. J Thorac Oncol. 2023; 18: 657-663.
3. Ramalingam SS, et al. Osimertinib after definitive chemoradiotherapy in patients with unresectable stage III epidermal growth factor receptor-mutated (EGFRm) NSCLC: primary results of the phase 3 LAURA study. Abstract LBA4, ASCO Annual Meeting 2024, 31 May–4 June, Chicago, IL, USA.

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Posted on 18 July 202419 July 2024