Osimertinib success in locally advanced EGFR-mutated NSCLC

Dr Suresh Ramalingam - Emory University School of Medicine, Atlanta, USA

We presented the results of the LAURA study at this meeting. This was a phase III clinical trial for patients with locally advanced stage 3 non-small cell lung cancer that’s considered surgically unresectable. The current standard of care for these patients is chemotherapy and radiation followed by one year of durvalumab immune checkpoint inhibitor. But we’ve known that for patients with EGFR mutation durvalumab and other PD-1/PD-L1 inhibitors do not provide benefit.

However, EGFR inhibitors may be beneficial because they have a mutation and small studies have suggested benefit. So we decided to conduct this trial to validate the role of osimertinib. Patients were enrolled with stage 3 unresectable disease with EGFR mutation after chemoradiation. They were enrolled within six weeks of chemotherapy and radiation as long as they did not have disease progression. They were randomised 2:1 to osimertinib versus placebo and the treatments were continued as long as they clinically benefitted from it.

The primary endpoint for the study was progression free survival which was assessed by independent radiographic review. At this point we’re happy to report that the median progression free survival was 39.1 months with osimertinib compared to 5.6 months with placebo. This was corresponding to a hazard ratio of 0.16 which means an 84% reduction in the risk of progression or death in patients.

We are able to report that the benefit was distributed across all key subgroups of patients enrolled to the study. We found a much lower likelihood of progression in the brain and to other parts of the body when patients were being treated with osimertinib. We didn’t see any undue safety signals with the use of osimertinib after chemoradiotherapy.

So, basically, we conclude by saying that the LAURA study for the first time establishes osimertinib as a new standard of care for patients after they have completed chemoradiotherapy in the setting of locally advanced non-small cell lung cancer.

What could be the impact of this research?

This will have, in my opinion, an immediate impact in the clinic because we see these patients complete chemoradiation and we often struggle what's the next step for them. We know that their cancer is unfortunately going to progress very quickly and now we have the option of offering them osimertinib which will have an immediate impact for patients.

It’s important now for us to test patients for EGFR mutation in stage 3 disease. Until now there was no reason to do molecular profiling for unresectable disease. The results of the LAURA study clearly emphasise the need for us to at least test for EGFR mutations so these patients can benefit from targeted therapy.