Preliminary experience of the concurrent use of radiosurgery and T-DM1 for brain metastases in HER2-positive metastatic breast cancer

Abstract

This is preliminary study assessing the efficacy and safety of concurrent use of radiation therapy (RT) and T-DM1 for the treatment of brain metastases (BM) in patients with HER2-positive metastatic breast cancer (BC). We retrospectively studied 12 patients treated for BM at the Institut Curie in 2014-2015 with T-DM1 and concurrent (4) or sequential (8) radiosurgery with or without whole brain irradiation. The following variables were studied: local control, clinical and radiological response as well as early and late side effects. The mean age of the population was 38 years at the time of diagnosis of BC and 46 years at of BM. All patients were with good PS. The response rate of the concurrent treatment group was 75 % with 1 complete response, 1 partial response, one stable disease and 1 progression. Comparatively, the response rate in the sequential group was as follows: two complete responses, two partial responses, six cases of stable disease and two cases of local progression. No patient experienced interruption of irradiation because of side effects. About 50 % of patients were asymptomatic after treatment. Radiation necrosis was observed in 50 % of patients in the concurrent group and 28.6 % of patients in the sequential group with a similar rate of oedema in the two groups. We found that the combination of T-DM1 and radiosurgery was feasible but can increase the incidence of radiation necrosis. Larger prospective studies with longer follow-up are needed to more clearly evaluate this association.

Adverse Events of Trastuzumab Emtansine (T-DM1) in the Treatment of HER2-Positive Breast Cancer Patients

“…The most commonly reported AEs in both groups was radiation necrosis (RN) with an incidence of 50% and 28.6%, for both T-DM1 during treatment and T-DM1 discontinued before SRS, respectively. Therefore, the combination of T-DM1 with SRS induced a clinically relevant increase in the risk of RN, when compared to previously published data [38][39][40]. Moreover, Carlson et al [40] found an association with cerebral swelling in patients on T-DM1 who underwent SRS.…”

“…Preliminary experience of the concurrent use of SRS and T-DM1 has recently been published [38]. Authors compared patients from 2 groups, patients who received T-DM1 during SRS and those with sequential treatment, where T-DM1 treatment was interrupted prior to SRS.…”

Combination of Trastuzumab Emtansine and Stereotactic Radiosurgery Results in High Rates of Clinically Significant Radionecrosis and Dysregulation of Aquaporin-4

“…Most patients underwent T-DM1 concurrent with any SRS treatment, though this was not always concurrent with the course of SRS, which later resulted in CSRN. A recent publication by Geraud and colleagues retrospectively reviewed 12 patients treated for brain metastases with T-DM1, four of whom received this concurrently with SRS and eight sequentially (10). In the concurrent group 50% of patients (2 patients) had radionecrosis as compared with only 28.6% in the sequential group.…”

“…Although both SRS and T-DM1 are important therapies for HER2 þ populations with brain metastases, a number of series, including a previous report from our institution, have suggested increased rates of clinically significant radionecrosis (CSRN) with their combination (9,10). Given clinical findings consistent primarily with edema, and the known role of Aquaporin-4 (Aqp4) in neuroinflammation, we further focused on Aqp4 changes after therapy.…”

Radio-sensitising effect of T-DM1 should not be discarded for the efficacy of radiosurgery in the management of brain metastases in patients with HER2-positive metastatic breast cancer

“…To the Editor, I want to congratulate Geraud et al [1] for their study. They evaluated the efficacy and safety of concurrent use of radiation therapy (RT) and T-DM1 for the treatment of brain metastases (BM) in patients with HER2-positive metastatic breast cancer (BC).…”