Tucatinib-based Regimen Shows Promise for Patients with Leptomeningeal Metastasis from HER2-Positive Breast Cancer: Study

A recent study has shown that a tucatinib-based regimen has demonstrated promise for patients with leptomeningeal metastasis from HER2-positive breast cancer. The nonrandomized TBCRC049 study assessed the tucatinib-based regimen’s effectiveness in treating leptomeningeal metastasis from HER2-positive breast cancer. The study demonstrated therapeutic levels of tucatinib and ONT-993 in the cerebrospinal fluid of all patients who received the combination. The regimen had a safety profile consistent with that observed in prior tucatinib studies, and the combination led to a median OS of 10 months.

Study Results

The study enrolled 17 patients, out of which 13 response-eligible patients experienced clinical benefit with the regimen. Among evaluable patients with target neurologic deficits at baseline (n = 12), 58% experienced an improvement of deficits, and 5 demonstrated stable target deficits as their best response. Six of the 7 patients with improved target deficits experienced this at their first restaging. Notably, no patients received steroids in the interval. Furthermore, all 13 response-eligible patients experienced clinical benefit with the regimen, including 8 who achieved stable disease and 4 partial responses (PRs), including 1 PR at cycle 3 that became a complete response (CR) by cycle 9. The leptomeningeal objective response rate (ORR) per composite criteria was 38%. Overall survival was also prolonged in this population, with 4 patients remaining alive at the time of last follow-up, which was July 21, 2021.

Patient-Reported Outcomes and QOL

The study also assessed patient-reported outcomes and QOL, and it showed that patients’ mean MD Anderson Symptom Inventory (MDASI) and Linear analogue self-assessment (LASA) scores improved over time, indicating an increase in QOL. To qualify for a leptomeningeal composite response, patients must have displayed improved or stable target deficits according to neurologic clinical evaluation, negative CSF cytology following a positive result at baseline, and radiologic PR or CR according to CNS imaging. Neurologic/clinical defined progression required a worsening of target deficits, negative or positive CSF cytology, and stable CNS imaging. Radiologic progression was defined as stable or worsened target deficits, negative or positive CNS cytology, and progressive disease. All participants completed the majority of MDASI and LASA questionnaires at all time points required.

Conclusion

The study concluded that this is the first prospective study to demonstrate the combination of intracranial response, improved symptoms, improved QOL, and extended survival from a systemic regimen in patients with leptomeningeal [disease] from breast cancer. As a result, systemic therapy is suggested as an initial approach for treating leptomeningeal [disease] from HER2-positive breast cancer. Tucatinib plus trastuzumab and capecitabine gained FDA approval in April 2020 for patients with HER2-positive breast cancer, including those with brain metastases, who were previously exposed to at least 1 HER2-based regimen in the metastatic setting.

Originally Post From https://www.onclive.com/view/tucatinib-based-regimen-improves-target-deficits-qol-in-her2-breast-cancer-with-leptomeningeal-metastasis

Read more about this topic at
Leptomeningeal carcinomatosis and breast cancer
Tucatinib-Based Regimen Improves Target Deficits, QOL in …