Brain metastases in NSCLC patients in the era of precision medicine

Background

The frequent occurrence of brain metastases (BM) in patients with advanced NSCLC represents a significant obstacle to long-term survival. The development of targeted therapies (TTs) in NSCLC along with compelling evidence suggesting that EGFR overexpansion might play a role in cancer metastasis mechanism to the brain makes their usage a very appealing substitution approach to available treatment options in neurooncology. However, the literature describing effects of TTs on brain lesions and microenvironment remains sparse. In addition, initial clinical developments of systemic treatments in NSCLC exclude patients with active BM. Using real world data, we are able to profile patients with BM from NSCLC including full molecular profile along with the effects of the EGFR Inhibitors.

Methods

This study used IMS Oncology Analyzer™, a syndicated, retrospective, longitudinal cancer treatment database, collecting anonymized patient-level oncology data in EU5, projected to national level. Data collected between 2006 - 2015 was used to profile BM patients and treatment effects with a special emphasis on anti EGFR therapies.

Results

Of the currently 607,437 treated population with BM, lung cancer accounts for 50%, followed by breast (14%), and melanoma (11%). NSCLC alone accounts for 34% from the entire currently treated population. 77% of the NSCLC with BM is non-squamous and 11% is EGFR mutated; mode age is between 61-65 years. 69 % of the studied population previously treated with EGFR inhibitors [erlotinib (ERL), gefitinib (GFT)], discontinued their therapy due to distant and/or local progression after on average 6.3 months while in patients with no BM it was on average 7.1 months. 10% of these patients were retreated with an EGFR inhibitor, either reversible (ERL, GFT) or irreversible (afatinib-based regimens, osimertinib). The remaining, received pemetrexed (28%), platinum-based therapies (9%), and chemotherapy alone (50%).

Conclusions

The usage of reversible EGFR inhibitors in BM patients from NSCLC has limited benefit and chemotherapy remains the treatment of choice after TTs failure. TTs which can penetrate the Blood-Brain Barrier today offer a new treatment option for BM patients, but further stratification of this patient segment is mandatory to drive clinical innovation.

Clinical trial identification

Legal entity responsible for the study

IMS Health

Funding

IMS Health

Disclosure

All authors have declared no conflicts of interest.