Osimertinib improves progression-free survival in patients with unresectable  stage III EGFR-mutated NSCLC that has been treated with chemoradiotherapy and may be a new standard of care for this population. 

The research was presented at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting, taking place May 31-June 4 in Chicago, Illinois.

“There are currently no approved targeted treatments specifically for unresectable stage III EGFRm NSCLC. With the superior efficacy results along with the robust magnitude of benefit in the LAURA study, osimertinib provides solution to a large unmet need for this patient population,” said lead study author Suresh Ramalingam, MD, FACP, FASCO, Winship Cancer Institute of Emory University, Atlanta, Georgia.

The international phase 3 LAURA trial enroled people with unresectable stage III NSCLC with EGFR mutations without any disease progression during/after definitive platinum-based chemoradiotherapy. 

People were randomly assigned on a two-to-one basis to receive osimertinib (143 patients) or a placebo (73 patients).

The median age of the participants was 62 years in the osimertinib arm and 64 years in the placebo arm. 

The majority of the participants were female (63% in the osimertinib arm, 58% in the placebo arm), Asian (81% in the osimertinib arm, 85% in the placebo arm), and had never smoked (63% in the osimertinib arm, 67% in the placebo arm).   

Key Findings

Osimertinib significantly improved progression-free survival (PFS) when compared with placebo. The median PFS was 39 months in the osimertinib group compared to 6 months with the placebo group.

In the osimertinib group, 74% of participants did not have any cancer growth after 12 months and 65% did not have any cancer growth after 24 months. This is compared with 22% and 13% in the placebo group, respectively.

Osimertinib showed a higher objective response rate, meaning the cancer was reduced in size by at least 30% with treatment, when compared with placebo (57% vs. 33%, respectively).

The rate of new metastases to the brain was lower in the osimertinib arm (8%) when compared with placebo (29%).

Researchers also compared subgroups, including differences in the type of chemoradiotherapy received and whether a patient had stage IIIA or IIIB/IIIC disease.

The PFS benefit seen for the osimertinib arm was found across all analysed subgroups. Of the participants who had disease progression in the placebo arm, 81% went on to take osimertinib. 

The adverse event profile of osimertinib was generally consistent with what has been noted in previous studies.

The most common side effects in both arms of the study were radiation pneumonitis (inflammation in the lungs caused by radiation therapy to the chest), diarrhoea, and rash. Most cases of radiation pneumonitis were mild to moderate. In the osimertinib arm, 13% of patients discontinued treatment due to adverse events compared with 5% in the placebo arm.

Next Steps

Researchers will continue to follow the participants to try to understand if osimertinib has an impact on overall survival, brain metastases, and other outcomes.  

Source: ASCO