Stereotactic radiosurgery with concurrent HER2-directed therapy is associated with improved objective response for breast cancer brain metastasis.

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Stereotactic radiosurgery with concurrent HER2-directed therapy is associated with improved objective response for breast cancer brain metastasis.

Neuro Oncol. 2019 Feb 06;:

Authors: Kim JM, Miller JA, Kotecha R, Chao ST, Ahluwalia MS, Peereboom DM, Mohammadi AM, Barnett GH, Murphy ES, Vogelbaum MA, Angelov L, Abraham J, Moore H, Budd GT, Suh JH

Abstract
Background: Patients with breast cancer positive for human epidermal growth factor receptor 2 (HER2) remain at high risk of intracranial relapse following treatment and experience increased rates of intracranial failure after stereotactic radiosurgery (SRS). We hypothesized that the addition of concurrent lapatinib to SRS would improve intracranial complete response rates.
Methods: Patients with newly diagnosed HER2-amplified breast cancer brain metastases from 2005-2014 who underwent SRS were included and divided into 2 cohorts based on timing of treatment with lapatinib. Outcome variables included the proportion of patients who achieved an intracranial complete response or progressive disease according to the RECIST 1.1 criteria, as well as individual lesion response rates, distant intracranial failure, and radiation necrosis.
Results: Eighty-four patients with 487 brain metastases met inclusion criteria during the study period. Over 138 treatment sessions, 132 lesions (27%) were treated with SRS and concurrent lapatinib, while 355 (73%) were treated with SRS without lapatinib. Compared with patients treated with SRS alone, patients treated with concurrent lapatinib had higher rates of complete response (35% vs 11%, P = 0.008). On a per-lesion basis, best objective response was superior in the concurrent lapatinib group (median 100% vs 70% reduction, P < 0.001). Concurrent lapatinib was not associated with an increased risk of grade 2+ radiation necrosis (1.0% with concurrent lapatinib vs 3.5% without, P = 0.27). Lapatinib had no protective effect on distant intracranial failure rates (48% vs 49%, P = 0.91).
Conclusion: The addition of concurrent lapatinib to SRS was associated with improved complete response rates among patients with HER2-positive brain metastases.
Key Points: 1.Complete response rates were higher with concurrent SRS and lapatinib compared with SRS alone. 2.Best objective response and complete response increased as lapatinib was administered closer to SRS. 3.There was no difference in the rate of radiation necrosis between the 2 cohorts.

PMID: 30726965 [PubMed - as supplied by publisher]

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