Dr O’Brien on Tucatinib Plus Trastuzumab/Capecitabine for Leptomeningeal Metastases in HER2+ Breast Cancer

Barbara Jane O’Brien, MD, associate professor of neuro-oncology, Department of Neuro-Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, discusses the investigation of tucatinib (Tukysa) in combination with trastuzumab (Herceptin) and capecitabine for the treatment of leptomeningeal metastases in patients with HER2-positive breast cancer.

O’Brien and colleagues presented findings from the phase 2 TBCRC049 study (NCT03501979) at 

. When the study was launched, enrollment was initially planned for 30 patients; however, enrollment closed at 17 patients following the April 2020 

FDA approval of this tucatinib-based combination

 for the treatment of patints with unresectable locally advanced or metastatic HER2-positive breast cancer, including those with brain metastases, following at least 1 prior anti-HER2-based regimen in the metastatic setting.

All 17 patients enrolled had evidence of leptomeningeal metastases on MRI; notably, 82% of patients also had brain metastases, and 65% received prior treatment for brain metastases. Eighty-eight percent of patients were symptomatic from leptomeningeal metastases.

Findings showed the leptomeningeal metastases objective response rate was 38% in evaluable patients (n = 13), and all patients in this population experienced a response or stable disease. O’Brien also explains that the median overall survival was approximately 10 months, which compared favorably with the historical control of 4.4 months.

Furthermore, 7 of 12 evaluable patients with target deficits at baseline experienced improvement following treatment. In this population who had deficits due to leptomeningeal metastases at baseline, no patients experienced a worsening of symptoms.

O'Brien notes that these findings underscore the need for further research to confirm this combination’s benefits in the treatment of leptomeningeal metastases in larger cohorts. These findings support the trend toward using systemic therapy as an initial approach in patients with leptomeningeal metastases from HER2-positive breast cancer, she concludes.

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Barbara Jane O’Brien, MD, discusses tucatinib plus trastuzumab and capecitabine for leptomeningeal metastases in HER2-positive breast cancer.

Dr O'Brien on Breast Cancer Research in Patients With HER2+ Brain Metastases

Barbara Jane O’Brien, MD, associate professor, Neuro-Oncology, Department of Neuro-Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, discusses the importance of expanding clinical trial enrollment criteria to include patients with HER2-positive breast cancer with brain metastases.

Historically, patients with HER2-positive breast cancer who have brain metastases, including leptomeningeal metastases, have been excluded from many breast cancer clinical trials, O’Brien begins. These patients comprise a unique subgroup with needs, response patterns, and treatment outcomes that are distinct from those of patients without brain metastases, O’Brien says. However, in the future, patients with breast cancer brain metastases should be included in more clinical trials, O’Brien emphasizes. The phase 2 HER2CLIMB trial (NCT02614794) is a prime example of a study that successfully evaluated an effective treatment option for patients with disease involvement in the central nervous system, O’Brien notes. Findings from this study supported the 

 (Tukysa) plus trastuzumab (Herceptin) and capecitabine (Xeloda) for the treatment of pretreated adult patients with advanced unresectable or metastatic HER2-positive breast cancer, including those with brain metastases. Hopefully, future clinical trials in breast cancer will enroll cohorts of patients with leptomeningeal metastases or solely evaluate therapies in this patient population, O’Brien concludes.

, O’Brien presented findings from the phase 2 TBCRC049 trial (NCT03501979), which investigated tucatinib plus trastuzumab and capecitabine in patients with HER2-positive breast cancer with leptomeningeal metastases. This trial enrolled 17 patients, all of whom had brain MRI evidence of leptomeningeal metastases. Eighty-two percent of patients also had brain metastases, and 65 of patients had received treatment for brain metastases. All 13 response-evaluable patients achieved clinical benefit with the regimen, and 5 achieved objective responses in their leptomeningeal metastases. Furthermore, 7 of 12 evaluable patients with target deficits at baseline had improved deficits with the treatment.

Barbara Jane O’Brien, MD, discusses expanding clinical trial enrollment criteria to include patients with HER2-positive breast cancer brain metastases.

Barbara Jane O’Brien, MD

Articles

Dr O’Brien on Tucatinib Plus Trastuzumab/Capecitabine for Leptomeningeal Metastases in HER2+ Breast Cancer

Dr O'Brien on Breast Cancer Research in Patients With HER2+ Brain Metastases