Summary: Medications commonly used to treat non-small cell lung cancer that has metastasized may have therapeutic benefits for patients with metastatic brain cancers.
Source: St. Michael’s Hospital
A medication commonly used to treat non-small cell lung cancer that has spread, or metastasized, may have benefits for patients with metastatic brain cancers, suggests a new review and analysis led by researchers at St. Michael’s Hospital of Unity Health Toronto and Harvard Medical School.
Published today in JAMA Network Open, the research hones in on osimertinib, a treatment recently approved in North America as a therapy for metastatic non-small cell lung cancer with a specific mutation.
In a meta-analysis of 15 studies with 324 patients, researchers found that 64 percent of patients with metastatic brain cancer whose cancer had spread from their lungs and were part of clinical trials with this therapy experienced a measurable response, and 90 percent experienced disease control in the central nervous system. Up to 40 percent of patients, however, reported severe side effects from the treatment.
“The development of brain metastases is an often feared complication of cancer,” said Anders Erickson, a graduate student at St. Michael’s Hospital in Dr. Sunit Das’ lab, who led this research.
“Cancers that spread to the brain have historically required radical treatment with surgery or radiation. Chemotherapies that are capable of killing cancer cells in the rest of the body are unable to penetrate the blood-brain barrier.”
There is a lack of evidence to support the use of targeted therapy – or small molecules that target the specific drivers of a cancer – in metastatic brain disease. The researchers set out to fill this gap by further analyzing whether this targeted treatment, known for its ability to cross the blood-brain barrier, might be beneficial to patients whose lung cancer had spread to the brain.
“Though more research is needed, our study supports the potential role this therapy could play for patients,” said Dr. Das, a scientist at the Keenan Research Centre for Biomedical Science and a neurosurgeon at St. Michael’s.
“It suggests we may one day be able to treat these patients without the concerns associated with surgery and radiation.”
The scientists aim to investigate this topic on a broader scale, looking at larger data sets to survey the impact of different targeted therapies for metastatic brain cancer.
“We hope our work will contribute to knowledge that will inform future treatment and move the needle for patients with metastatic brain cancer in the era of precision medicine,” Erickson said.
St. Michael’s Hospital
Ana Gajic – St. Michael’s Hospital
The imageis in the public domain.
Original Research: Open access
“Assessment of Effectiveness and Safety of Osimertinib for Patients With Intracranial Metastatic Disease: A Systematic Review and Meta-analysis”. Anders W. Erickson, BS; Priscilla K. Brastianos, MD; Sunit Das, MD, PhD.
JAMA Network Open doi:10.1001/jamanetworkopen.2020.1617.
Assessment of Effectiveness and Safety of Osimertinib for Patients With Intracranial Metastatic Disease: A Systematic Review and Meta-analysis
Intracranial metastatic disease (IMD) is a serious and life-altering complication for many patients with cancer. Targeted therapy may address the limitations of current treatments as an additional agent to achieve intracranial disease control in some patients with IMD. Given the paucity of evidence regarding effectiveness, current guidelines have not made recommendations on the use of targeted therapy. Osimertinib mesylate is a mutant epidermal growth factor receptor (EGFR) inhibitor that can penetrate the blood-brain barrier and inhibit tumor cell survival and proliferation in patients with non–small cell lung cancer (NSCLC) with specific EGFR alterations.
To assess the effectiveness and safety of osimertinib in the management of IMD.
Studies were selected from MEDLINE and Embase databases from their inception to September 20, 2019, using the following search query: (osimertinib OR mereletinib OR tagrisso OR tamarix OR azd9291) AND (brain metastases OR intracranial metastatic disease OR cns).
Studies reporting intracranial outcomes for patients with metastatic EGFR-variant NSCLC and IMD treated with osimertinib were included in this systematic review and meta-analysis. Among 271 records identified in the systematic review, 15 studies fulfilled eligibility criteria for inclusion in the meta-analysis.
Data Extraction and Synthesis
Data were extracted from published studies and supplements. These data were pooled using a random-effects model. Risk of bias was assessed using the Cochrane risk of bias tool and the modified Newcastle-Ottawa Scale.
Main Outcomes and Measures
Information extracted included study characteristics, intracranial effectiveness measures, and safety measures. Meta-analyses of proportions were conducted to pool estimates for central nervous system (CNS) objective response rate and CNS disease control rate.
Fifteen studies reporting on 324 patients were included in the meta-analysis. The CNS objective response rate was 64% (95% CI, 53%-76%; n = 195), and CNS disease control rate was 90% (95% CI, 85%-93%; n = 246). Included studies reported complete intracranial response rates of 7% to 23%, median best decrease in intracranial lesion size of −40% to −64%, and Common Terminology Criteria for Adverse Events (version 3.0) grade 3 or higher adverse event rates of 19% to 39%. Subgroup analyses did not reveal additional sources of heterogeneity.
Conclusions and Relevance
Findings reported herein support a potential role for osimertinib in the treatment of patients with metastatic EGFR-variant NSCLC and IMD treated with osimertinib. Clinical decision makers would benefit from the inclusion of patients with IMD in future trials to identify factors that predict responses to targeted therapy.