Clinical outcome of patients with isolated central nervous system progression on first-line Pertuzumab and Trastuzumab treatment for HER2-positive metastatic breast cancer in a real life cohort.

Abstract PurposeMore than 10% of HER2-positive metastatic breast cancer (mBC) will develop Central Nervous System (CNS) metastases as first and isolated site of relapse on trastuzumab and pertuzumab first line therapy. However, few clinical data are available to guide the best strategy in this setting.MethodsPatients experiencing isolated CNS progression on trastuzumab and pertuzumab first line therapy were retrospectively identified from the French Epidemiological Strategy and Medical Economics (ESME) real life database between 2008 and 2016. ResultsAmong 995 patients treated with first line trastuzumab and pertuzumab for HER2-positive mBC, 132 patients (13%) experienced isolated CNS progression with a median time of 12 months after mBC diagnosis. Twelves patients did not received any treatment and were excluded from the analysis. Among the 120 patients considered, 76 (63%) received CNS-directed local therapy, 73 (60%) continued trastuzumab and pertuzumab whereas 47 (39%) started another systemic treatment. After a median follow up of 21 months, there was no difference in progression free survival for patient who continued trastuzumab-pertuzumab or switched to another systemic treatment. In multivariate analysis, trastuzumab-pertuzumab continuation was associated with longer OS (HR 0,28 IC95%: 0,14-0,54 p<0,001). mOS was not reached (95% 37.6-NE) and was 23.2 months (95%CI 15.5-53.6) in patients who continued trastuzumab and pertuzumab therapy and in patients who switched for another systemic therapy, respectively.ConclusionIn this real-life cohort, trastuzumab-pertuzumab continuation after local treatment for isolated CNS progression did not negatively impact PFS and OS. Prospective trials and assessment of new strategies are warranted in this specific situation.