Osimertinib Offers New Standard of Care in Stage III EGFR-Mutated NSCLC
Suresh S. Ramalingam, MD, discussed the practice-changing findings and implications of the phase 3 LAURA study investigating osimertinib for the treatment of patients with EGFR-mutated non–small cell lung cancer.
Lung with cancer cells: © catalin - stock.adobe.com
The phase 3 LAURA study (NCT03521154) showed that the drug osimertinib (Tagrisso) significantly extends survival for patients with unresectable stage III non–small cell lung cancer (NSCLC) with EGFR mutations, a patient group that had previously received a standard treatment of chemotherapy and radiation.
LAURA compared osimertinib with placebo in 216 patients. Results showed a dramatic improvement in progression-free survival (PFS) for those taking osimertinib with 39.1 months (95% CI, 31.5-not calculable) vs 5.6 months (95% CI, 3.7-7.4). The 12-month PFS rate was 74% with osimertinib vs 22% with placebo, and the 24-month PFS rates were 65% vs 13%, respectively.
While overall survival data is still being collected, early results suggest a potential benefit for osimertinib in this area. The drug was generally well-tolerated, with the most common adverse effect being lung inflammation.
Based on these findings, osimertinib could now be considered the new standard of care for this specific group of lung cancer patients.
In an interview with Targeted OncologyTM, Suresh S. Ramalingam, MD, FACP, FASCO, executive director of the Winship Cancer Institute of Emory University and first author of the LAURA study, discussed the implications of these practice-changing findings.
Suresh S. Ramalingam, MD, FACP, FASCO
Targeted Oncology: What are some of the unmet needs in this patient population?
Ramalingam: The LAURA study focused on patients with stage III non–small cell lung cancer for whom the disease was considered surgically unresectable and specifically for patients with an EGFR mutation. For this group of patients, presently, concurrent chemoradiation followed by immunotherapy has been the standard of care. But that is not something that works well for patients with an EGFR mutation. That is why we conducted the LAURA study. If a patient had stage III disease that can be removed surgically and they had an EGFR mutation, these data are applicable directly to them.
What are the key findings that were presented from LAURA?
The study included patients who had stage III disease with either EGFR exon 19 or 21 mutations, which are the 2 most common types of EGFR mutations, and these patients had completed chemotherapy and radiation. [If] their cancer had not progressed, they were randomized to osimertinib or placebo. The primary end point was progression-free survival.
We are delighted to report that the median progression-free survival was substantially better for patients treated with osimertinib. It was 39.1 months compared [with] 5.6 months for patients in the placebo group, the hazard ratio was 0.16, and it was statistically significant. We also found that the benefit was seen across all key subgroups of patients enrolled to the study, so it is widely applicable to this patient population, regardless of age, gender, specific type of mutation, where they come from, and so forth.
We saw that the safety profile was consistent with what we would expect with osimertinib alone or for patients who had recently completed chemoradiation therapy. There were no undue safety signals. The survival results at this point are not mature, but we see a promising trend benefiting osimertinib. Overall, we believe this trial will change the standard of care for this subset of patients.
What are the implications of these findings going forward with this treatment option compared with what is presently available?
I believe that this will have an immediate impact on management of patients who have stage III locally advanced EGFR-mutated lung cancer, because for these patients, right now, we do chemotherapy and radiation, and we just follow them. The LAURA study showed that if they do not get any further therapy, within 5 to 6 months, half the patients have disease progression. Using osimertinib in the setting, a drug that is approved and available for stage IV disease and for earlier resected lung cancer, would be an easy integration into standard treatment algorithms.
What do you see as the next step for research in this area?
Now that osimertinib part of treatment for every stage of non–small cell lung cancer, I think the next step would be to build on the benefit of osimertinib and develop novel combination approaches, understanding osimertinib’s mechanisms, which we have a good sense of, and developing novel approaches to overcome resistance are going to be important.
It is an exciting time for patients with lung cancer because of the availability of targeted and immunotherapy treatment options. We are seeing improvement in patients with non–small cell lung cancer. Overall, patients with lung cancer are living better and living longer, and that is thanks to the amazing therapeutic advances that have been made in the past few years.
