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Assessing the Association of Targeted Therapy and Intracranial Metastatic Disease
Anders W Erickson1,2, Steven Habbous2, Frances Wright2,3
1Institute of Medical Science, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada.
Importance:
Targeted therapies have been hypothesized to prolong survival in the treatment of patients with intracranial metastatic disease (IMD) but, paradoxically, increase IMD incidence by improving systemic disease control and prolonging survival from the primary tumor. The real-world benefits of targeted therapy in treating patients with IMD are unclear, as clinical trials have excluded patients with IMD and lacked end points that report intracranial outcomes.
Objective:
To assess the association of targeted therapy and IMD with patient survival.
Design, Setting, And Participants:
This retrospective cohort study included all patients in Ontario, Canada, who received a diagnosis of IMD from April 2005 to January 2018 with primary diagnoses of breast cancer, lung or bronchus cancer, or melanoma and control patients who were matched by primary disease without IMD. The data were analyzed between March and October 2020.
Exposures:
EGFR-, ERBB2 (HER2-), or BRAF-targeted therapy or IMD status.
Main Outcomes And Measures:
Kaplan-Meier and multivariable Cox regression analyses were performed to compare overall survival (OS) between patient subcohorts divided by primary disease and stratified by targeted therapy receipt or IMD status.
Results:
In this cohort of 26 676 patients with IMD and breast cancer, lung and bronchus cancer, or melanoma, 57% of patients were women, and the median age at IMD diagnosis was 64 years (interquartile range, 56-72 years). Post-IMD targeted therapy was associated with prolonged OS in patients with ERBB2-positive breast cancer (hazard ratio [HR], 0.41; 95% CI, 0.33-0.50), EGFR-positive lung cancer (HR, 0.28; 95% CI, 0.23-0.34), and BRAF-positive melanoma (HR, 0.20; 95% CI, 0.14-0.29) compared with those who did not receive post-IMD targeted therapy. The presence of IMD was associated with shorter OS in patients with metastatic ERBB2-positive breast cancer (HR, 1.80; 95% CI, 1.56-2.08) and metastatic EGFR-positive lung cancer (HR, 1.22; 95% CI, 1.08-1.39) but not metastatic BRAF-positive melanoma (HR, 1.11; 95% CI, 0.77-1.61) compared with those without IMD.
Conclusions And Relevance:
The findings of this cohort study suggest an association between real-world use of targeted therapies and prolonged OS in patients with IMD in the setting of ERBB2-positive breast cancer, EGFR-positive lung cancer, and BRAF-positive melanoma. Including patients with IMD in clinical trials and using end points that interrogate IMD will be critical to determine the role of targeted therapies in treating patients with IMD.
Insights
Targeted therapies improved survival for patients with intracranial metastatic disease (IMD) and specific cancers, including ERBB2-positive breast, EGFR-positive lung, and BRAF-positive melanoma. Further research including IMD in clinical trials is crucial.
Area of Science:
- Oncology
- Medical Science
- Clinical Research
Background:
- Intracranial metastatic disease (IMD) poses unique challenges in cancer care.
- The role of targeted therapies in patients with IMD remains unclear due to trial exclusions and endpoint limitations.
Purpose of the Study:
- To evaluate the association between targeted therapy use and overall survival (OS) in patients diagnosed with IMD.
- To assess the impact of IMD on OS in patients with specific primary cancers.
Main Methods:
- Retrospective cohort study of 26,676 patients in Ontario, Canada (April 2005-January 2018) with IMD from breast, lung, or melanoma.
- Analysis compared OS between patients receiving EGFR-, ERBB2-, or BRAF-targeted therapy versus those who did not.
- Kaplan-Meier and Cox regression analyses were used to determine survival associations.
Main Results:
- Post-IMD targeted therapy was linked to longer OS in ERBB2-positive breast cancer (HR, 0.41), EGFR-positive lung cancer (HR, 0.28), and BRAF-positive melanoma (HR, 0.20).
- IMD presence was associated with shorter OS in metastatic ERBB2-positive breast cancer (HR, 1.80) and EGFR-positive lung cancer (HR, 1.22).
- No significant association between IMD and OS was found in metastatic BRAF-positive melanoma (HR, 1.11).
Conclusions:
- Real-world targeted therapy use is associated with prolonged OS in specific IMD patient groups.
- Future clinical trials must include IMD patients and intracranial endpoints to clarify targeted therapy's role.
- Findings highlight the potential benefit of targeted agents in managing specific intracranial metastases.
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