Osimertinib Supported For Intracranial Metastases In NSCLC

Author: By Lynda Williams, Senior medwireNews Reporter 

medwireNews: Findings from a systematic review and meta-analysis published in JAMA Network Open suggest that osimertinib may be a feasible therapy for EGFR mutation-positive non-small-cell lung cancer (NSCLC) patients with intracranial metastases.  

Sunit Das, from the University of Toronto in Ontario, Canada, and co-authors collated data from 324 patients who participated in 15 clinical trials or studies of osimertinib, including AURA3 and FLAURA. 

They calculated a central nervous system (CNS) objective response rate of 64% among 195 patients with “high” heterogeneity based on available information, while the CNS disease control rate was 90% among 246 patients but showed “low” heterogeneity. 

The median best decrease in intracranial lesions ranged from 40% to 64%, while a complete intracranial response occurred in between 7% and 23% of patients. 

Median CNS progression-free survival was recorded in two studies as 10.9 and 11.7 months, respectively, and reported as not reached in seven studies. The median CNS duration of response in five studies was reported as between 8.9 and 15.2 months and four studies reported time to CNS response, of between 1.3 and 1.5 months. 

Median overall survival was reported in one study as 16.2 months, and in three studies as not reached, Sunit Das et al say. 

Safety outcomes were reported for seven studies, with grade 3 and more severe adverse events occurring in 19% to 39% of patients, which the investigators compare against reported rates of between 3% for afatinib to 84% for bevacizumab plus paclitaxel and carboplatin. 

Two fatal toxicity events linked to osimertinib were identified, namely pneumonitis and interstitial lung disease.  

The authors say their “results support a potential role for osimertinib” in this population but admit that “it is unclear whether that may be as an adjunct therapy or a nonadjuvant therapy or as a replacement for standard frontline therapies, such as neurosurgery or radiotherapy.” 

They conclude: “Trials in oncology should continue to include patients with [intracranial metastatic disease] to clarify the use of novel therapies for these individuals. 

“Advances in tumor genotyping and subgroup analyses from large trials may better assess responses to targeted therapies on an individual patient basis and more precisely define the role of osimertinib and other targeted therapies in [intracranial metastatic disease] management.” 

Reference  

Erickson AW, Brastianos PK, Das S. Assessment of effectiveness and safety of osimertinib for patients with intracranial metastatic disease. A systematic review and meta-analysis. JAMA Netw Open; 3: e201617, published online 25 March 2020. doi:10.1001/jamanetworkopen.2020.1617