Why a Targeted Therapy is Better Than Immunotherapy for Some Patients with Inoperable Non-Small Cell Lung Cancer

Non-small cell lung cancer (NSCLC), with an epidermal growth factor receptor (EGFR) mutation, tends not to respond well to immunotherapy treatments, including durvalumab. However, Yale Cancer Center (YCC) researchers recently reported in the Journal of Thoracic Oncology that the targeted therapy osimertinib, when administered after chemotherapy and radiation, is associated with significantly improved progression-free survival (living without the cancer worsening).

“Osimertinib is a drug that is actually very specific for the EGFR mutation itself,” said Amin Nassar, MD, co-first author on the study, clinical fellow, and member of YCC. “It has proven to be very efficacious in the stage IV setting and also, more recently with the ADAURA trial, in the stage III setting. We wanted to find out in the unresectable [tumor not removable with surgery] stage III population, are we going to see similar benefits? And is this targeted therapy actually better than immunotherapy for these specific patients?”

The retrospective study, using data from 2015 through 2022, involved 136 stage III NSCLC patients with the EGFRmutation. Researchers compared the survival outcomes achieved after taking durvalumab, osimertinib, or neither treatment (i.e. observation alone) after chemotherapy and radiation. They discovered that 86% of patients being treated with osimertinib lived at least two years without the disease worsening. This was significantly higher than patients who were treated with durvalumab (30%) and patients who took neither treatment (27%).

There were severe side effects associated with only 6% of patients treated with osimertinib, compared with 18% of patients treated with durvalumab. The most common side effect was pneumonitis, but researchers found no unexpected safety risks during the study.

Nassar said there need to be larger studies to determine the overall survival benefit of osimertinib as a post-remission therapy (consolidation therapy) for this unresectable, NSCLC EGFR-mutant patient population.

“In the ADAURA trial , patients with resectable stage III NSCLC receive surgical resection followed by chemotherapy and then osimertinib. With that, they achieve not only better progression-free survival but also overall survival. That’s the current standard of care,” said Nassar. “However, in the unresectable population, this is the only data we have right now that shows that there is also a progression-free survival benefit when treated with osimertinib for these stage III NSCLC patients with the EGFR mutation. We expect to see preliminary results from the LAURA study in the next couple of months. The question will be, is there an overall survival benefit as well?”

Yale Cancer Center’s So Yeon Kim joined Nassar as a co-first author and Sarah Goldberg from Yale Cancer Center was a co-senior author.