Study Shows First Evidence of Effective Systemic Therapy for HER2+ Breast Cancer With LM

An investigator-initiated phase 2 study (NCT03501979) investigated the combination of tucatinib (Tukysa), trastuzumab, and capectiabine for treating leptomeningeal metastasis (LM), a spread of cancer to the membranes surrounding the brain and spinal cord, in patients with HER2-positive breast cancer.

Previously, treatment options for LM were limited, and prognosis was poor. This drug combination is already approved for a similar type of breast cancer but without LM involvement.

The study enrolled 17 patients instead of the planned 30. Most patients had symptoms and some had abnormal spinal fluid analysis.

The treatment showed promising results. Over a third of patients achieved an objective response. All patients experienced some clinical benefit, including stable disease or improvement. Many patients with initial neurological problems showed improvement. Further, quality of life and symptom burden significantly improved for most patients, and patients lived longer than expected with this type of cancer.

This is the first study to show clear benefits of a systemic drug treatment for LM in HER2-positive breast cancer. These findings suggest that treating LM with systemic therapy might be a better initial approach than previously used methods.

Here, Barbara O'Brien, MD, associate professor of neuro-oncology at MD Anderson Cancer Center, who presented findings from the study at the 2024 American Society of Clinical Oncology Annual Meeting, discusses the goals and results.

Transcription:

0:05 | Our study evaluated the HER2-directed TKI tucatinib with trastuzumab and capecitabine in patients with HER2-positive breast cancer and leptomeningeal metastasis that was newly diagnosed, and our primary end point was overall survival. And we were also looking at CSF pharmacokinetics, as well as response assessment, symptoms, and quality of life.

0:34 | The study initially enrolled robustly, but no longer enrolled patients to tucatinib when it became FDA approved. And so the 17 patients that were involved, we found a median overall survival of 10 months, which compared favorably to the historic control of 4.4 months. So this was previously reported. Now we're reporting on our response response data. And we found that over a third of patients achieved a composite leptomeningeal response. And also the majority of patients had improvement of their symptoms that were present at baseline.

Transcription created with AI and edited for clarity.