Assessing the Association of Targeted Therapy and Intracranial Metastatic Disease

Abstract INTRODUCTION Intracranial metastatic disease (IMD) is a serious and life-altering complication for many patients with cancer. Targeted therapy may address limitations of current treatments as an additional agent to achieve intracranial disease control in some patients with IMD. Osimertinib 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 mutations. The purpose of this study is to assess the efficacy and safety of osimertinib in the management of IMD. METHODS Studies reporting intracranial outcomes for patients with EGFR-mutant NSCLC and IMD treated with osimertinib were included. Among 271 records identified in MEDLINE and EMBASE, 15 studies fulfilled eligibility criteria. Outcomes were pooled using a random-effects model. Risk of bias was assessed using the Cochrane Risk of Bias tool and modified Newcastle-Ottawa scale. Information extracted included study characteristics, intracranial efficacy measures, and safety measures. Meta-analyses were conducted to pool applicable outcomes. RESULTS 15 studies reporting on 324 patients were included in the analysis. Combined CNS ORR and CNS DCR were calculated to be 64% (95% CI, 53–76%; n = 195), and 90% (95% CI, 85–93%; n = 246). Risk ratios for CNS ORR and CNS DCR were calculated to be 1.44 (95% CI, 1.06–1.96; n = 52) and 1.13 (95% CI, 0.96–1.33; n = 52). Included studies reported complete intracranial response rates of 7–23%, median best decrease in intracranial lesion size of 40–64%, and grade 3+ adverse event rates of 19–39%. CONCLUSIONS Findings reported here support a potential role for osimertinib for patients with EGFR-mutant NSCLC and IMD. Clinical decision-makers would benefit from the inclusion of patients with IMD in future trials to identify factors that predict responses to targeted therapy.

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The Impact of Targeted Therapy on Intracranial Metastatic Disease Incidence and Survival

Frontiers in Oncology ◽

10.3389/fonc.2019.00797 ◽

2019 ◽

Vol 9 ◽

Author(s):

Anders W. Erickson ◽

Sunit Das

Keyword(s):

Targeted Therapy ◽

Metastatic Disease ◽

Disease Incidence ◽

The Impact ◽

Intracranial Metastatic Disease

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HER2-targeted therapy prolongs survival in patients with HER2-positive breast cancer and intracranial metastatic disease: a systematic review and meta-analysis

Neuro-Oncology Advances ◽

10.1093/noajnl/vdaa136 ◽

2020 ◽

Vol 2 (1) ◽

Author(s):

Anders W Erickson ◽

Farinaz Ghodrati ◽

Steven Habbous ◽

Katarzyna J Jerzak ◽

Arjun Sahgal ◽

...

Keyword(s):

Breast Cancer ◽

Targeted Therapy ◽

Metastatic Disease ◽

Response Rate ◽

Meta Analysis ◽

Adverse Event Rate ◽

Her2 Positive ◽

Her2 Positive Breast Cancer ◽

Intracranial Metastatic Disease ◽

Positive Breast Cancer

Abstract Background Intracranial metastatic disease (IMD) is a serious and known complication of human epidermal growth factor receptor 2 (HER2)-positive breast cancer. The role of targeted therapy for patients with HER2-positive breast cancer and IMD remains unclear. In this study, we sought to evaluate the effect of HER2-targeted therapy on IMD from HER2-positive breast cancer. Methods We searched MEDLINE, EMBASE, CENTRAL, and gray literature sources for interventional and observational studies reporting survival, response, and safety outcomes for patients with IMD receiving HER2-targeted therapy. We pooled outcomes through meta-analysis and examined confounder effects through forest plot stratification and meta-regression. Evidence quality was evaluated using GRADE (PROSPERO CRD42020161209). Results A total of 97 studies (37 interventional and 60 observational) were included. HER2-targeted therapy was associated with prolonged overall survival (hazard ratio [HR] 0.47; 95% confidence interval [CI], 0.39–0.56) without significantly prolonged progression-free survival (HR 0.52; 95% CI, 0.27–1.02) versus non-targeted therapy; the intracranial objective response rate was 19% (95% CI, 12–27%), intracranial disease control rate 62% (95% CI, 55–69%), intracranial complete response rate 0% (95% CI, 0–0.01%), and grade 3+ adverse event rate 26% (95% CI, 11–45%). Risk of bias was high in 40% (39/97) of studies. Conclusion These findings support a potential role for systemic HER2-targeted therapy in the treatment of patients with IMD from HER2-positive metastatic breast cancer.

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