Patients With EGFR-Mutant NSCLC May Benefit from Targeted Therapy More Than Checkpoint Inhibitors

An estimated 10 to 15% of non-small cell lung cancers harbor EGFR mutations.

Immunotherapy has changed the way lung cancer is treated in many patients. But as the use of these drugs expands—including to patients with earlier stages of the disease—it’s become increasingly apparent that some patients benefit more than others. To ensure that every patient gets the most appropriate treatment, it’s important to further refine the field of personalized medicine and the understanding of how the molecular signatures of lung cancer affect patient outcomes.

A recent retrospective, multicenter cohort study focused on whether patients with unresectable, stage 3, EGFR-mutant non-small cell lung cancer (NSCLC) were more likely to benefit from immunotherapy or targeted therapy following standard treatment. The researchers, including Brigham and Women’s Hospital investigators, found that in this cohort of patients, the targeted therapy osimertinib was more effective than the immunotherapy durvalumab at increasing progression-free survival (PFS), without added toxicity.

“Some studies, including the PACIFIC trial, have suggested that patients with EGFR-mutant lung cancer don’t benefit from durvalumab the same way that patients without a mutation do,” says Elio Adib, MD, a resident in radiation oncology at the Brigham and a co-senior author of the study, published in the Journal of Thoracic Oncology. “We decided to review data that might help determine whether there are better treatment options for consolidation therapy in this patient group.”

An estimated 10 to 15% of NSCLC cases harbor EGFR mutations.

Comparing Osimertinib to Durvalumab

Standard treatment for unresectable, stage III NSCLC is a combination of chemotherapy and radiation. Use of the checkpoint inhibitor drug durvalumab as a consolidation therapy after standard treatment has been shown to improve survival, but the best treatment option for patients with EGFR-mutant NSCLC has not been studied. Osimertinib, a third-generation tyrosine kinase inhibitor that targets EGFR, is currently approved for stage IV NSCLC and is being studied in patients with earlier-stage disease.

In this study, investigators evaluated outcomes for 136 patients with EGFR-mutant NSCLC treated across 24 institutions in North America, Europe, and the Middle East.

“This is a very specific patient population, so we reached out to a broad range of providers,” Dr. Adib explains. “It was important for us to get more information about this group of patients and how they fared since we still have no information about this treatment approach in the context of a prospective clinical trial.”

Osimertinib Leads to Longer Progression-Free Survival

The evaluation included 56 patients who received consolidation durvalumab—33 who received consolidation osimertinib and 47 who received observation alone following standard chemoradiation. The investigators found that patients treated with osimertinib had significantly longer PFS than either durvalumab or observation alone; in fact, the checkpoint inhibitor group and the observation group had similar PFS.

After adjusting for lymph node status, the investigators found that 86% of patients receiving osimertinib had no progression over 24 months, compared with 30% of those who received durvalumab and 27% of those who had observation. No differences in overall survival were observed, potentially due to the short duration of median follow-up (46 months).

“Although prospective clinical trials, like the LAURA trial, are needed to confirm these findings, the study suggests that osimertinib is more likely to benefit NSCLC patients with EGFR mutations than these other approaches,” Dr. Adib says. “This is something we hope to study.”