Targeted Therapy After Chemoradiation for Unresectable Stage III NSCLC

For patients with unresectable stage III non–small-cell lung cancer (NSCLC), consolidation durvalumab is the standard of care after chemoradiation for those who do not experience progression. However, the benefit of durvalumab consolidation is unclear for patients who harbor EGFR mutations; the estimated prevalence of EGFR mutations is 10% to 50% depending on demographics, such as ethnicity and smoking history.

Now, researchers report results from the LAURA trial, the first phase 3 study to assess a targeted therapy following chemoradiotherapy in these patients. In the industry-sponsored, global trial, 216 adult patients with locally advanced, unresectable stage III NSCLC harboring an EGFR exon 19 deletion or L858R mutation who did not experience progression following definitive chemoradiotherapy were randomized to either osimertinib or placebo. Treatment continued until progression or unacceptable toxicity. Importantly, patients in both arms were allowed to receive osimertinib following confirmed disease progression.

Progression-free survival (PFS), the primary endpoint, was significantly improved with osimertinib compared with placebo (median, 39.1 vs. 5.6 months; hazard ratio, 0.16; P<0.001). In addition, although overall survival data were only 20% mature, there was a trend to improved 36-month OS in the osimertinib group, despite crossover (84% vs. 74%; HR, 0.8; 95% CI, 0.42–1.56; P=0.53). No new safety signals were noted with osimertinib, and toxicities were mostly mild and did not lead to treatment discontinuation.