The phase 2 TBCRC049 study (NCT03501979) has revealed encouraging results for patients with HER2-positive breast cancer and leptomeningeal metastasis treated with a combination of tucatinib (Tukysa), trastuzumab (Herceptin), and capecitabine. Leptomeningeal metastasis, a condition where cancer cells spread to the brain and spinal cord, is associated with a poor prognosis and limited treatment options. The study, led by Barbara O'Brien, MD, of MD Anderson Cancer Center, suggests this regimen could offer a valuable treatment option for this patient population.
Study Details and Findings
The TBCRC049 study evaluated the efficacy of the HER2-directed tyrosine kinase inhibitor tucatinib, combined with trastuzumab and capecitabine, in patients with newly diagnosed leptomeningeal metastasis from HER2-positive breast cancer. The primary endpoint was overall survival, with secondary endpoints including cerebrospinal fluid pharmacokinetics, response assessment, symptom improvement, and quality of life.
Results from the study, which included 17 patients, showed a median overall survival of 10 months, significantly longer than the historical control of 4.4 months. Furthermore, over one-third of patients achieved a composite leptomeningeal response, and the majority experienced improvement in their baseline symptoms.
Insights from Dr. O'Brien
Dr. O'Brien highlighted the unmet needs in treating leptomeningeal metastasis, emphasizing the lack of standard treatment options and the associated neurologic decline and poor prognosis. She noted that while the tucatinib regimen offers a "glimmer of hope," further research is needed to improve the durability of response. Potential strategies include combining tucatinib with other systemic or intrathecal agents and optimizing the sequencing of treatments.
The Importance of Inclusion in Clinical Trials
Historically, patients with brain metastasis and leptomeningeal metastasis have often been excluded from breast cancer trials. Dr. O'Brien stressed the importance of including these patients in future trials, as was done in the pivotal HER2CLIMB study (NCT02614794). She advocated for dedicated cohorts and open trials specifically for patients with leptomeningeal metastasis to address their unique needs and improve treatment outcomes.
