Real-World Survival Outcomes With Targeted Therapy for Intracranial Metastatic Disease

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In a retrospective cohort study reported in JAMA Oncology, Erickson et al found that real-world use of targeted therapy after diagnosis of intracranial metastatic disease was associated with improved overall survival vs no use of targeted therapy in patients with HER2-positive breast cancer, EGFR-mutant lung/bronchus cancer, and BRAF-mutant melanoma.

As stated by the investigators, “Targeted therapies have been hypothesized to prolong survival in the treatment of patients with [intracranial metastatic disease] but, paradoxically, increase [intracranial metastatic disease] incidence by improving systemic disease control and prolonging survival from the primary tumor. The real-world benefits of targeted therapy in treating patients with [intracranial metastatic disease] are unclear, as clinical trials have excluded patients with [intracranial metastatic disease] and lacked endpoints that report intracranial outcomes.”

Study Details

The study included all patients in Ontario who received a diagnosis of intracranial metastatic disease from April 2005 to January 2018 with primary diagnoses of breast cancer, lung/bronchus cancer, or melanoma who did or did not receive targeted therapy post–intracranial metastatic disease diagnosis and control patients without intracranial metastatic disease matched by primary disease. Data were analyzed between March and October 2020.

Key Findings

Among patients with HER2-positive breast cancer who did (n = 314) vs did not (n = 468) receive HER2-targetd therapy post–intracranial metastatic disease, median overall survival was 17.02 months vs 2.17 months (hazard ratio [HR] = 0.41, 95% confidence interval [CI] = 0.33–0.50).

Among patients with EGFR-mutant lung/bronchus cancer who did (n = 415) vs did not (n = 278) receive EGFR-targeted therapy post–intracranial metastatic disease, median overall survival was 14.82 months vs 0.95 months (HR = 0.28, 95% CI = 0.23–0.34).

Among patients with BRAF-mutant melanoma who did (n = 93) vs did not (n = 79) receive BRAF-targeted therapy post–intracranial metastatic disease, median overall survival was 8.97 months vs 0.92 months (HR = 0.20, 95% CI = 0.14–0.29).

Compared with no intracranial metastatic disease, the presence of intracranial metastatic disease among patients with stage IV disease was associated with shorter overall survival among those with HER2-positive breast cancer (HR = 1.80, 95% CI = 1.56–2.08) and EGFR-mutant lung/bronchus cancer (HR = 1.22, 95% CI = 1.08–1.39), but not among those with BRAF-mutant melanoma (HR = 1.11, 95% CI = 0.77–1.61).

The investigators concluded: “The findings of this cohort study suggest an association between real-world use of targeted therapies and prolonged overall survival in patients with [intracranial metastatic disease] in the setting of [HER2]-positive breast cancer, EGFR-positive lung cancer, and BRAF-positive melanoma. Including patients with [intracranial metastatic disease] in clinical trials and using endpoints that interrogate [intracranial metastatic disease] will be critical to determine the role of targeted therapies in treating patients with [intracranial metastatic disease].”

Sunit Das, MD, PhD, of St. Michael’s Hospital, University of Toronto, is the corresponding author for the JAMA Oncology article.

Disclosure: The study was supported by the Ontario Ministry of Health and Long-Term Care and others. For full disclosures of the study authors, visit

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.