M. Carton (Saint-Cloud, France)

Institut Curie

Author Of 2 Presentations

 On-Demand ePoster Display

102P - Breast cancer patients treated with intrathecal therapy for leptomeningeal metastases: characteristics and validation of prognostic models in a large real-life database

Abstract

Background

Leptomeningeal metastasis (LM) is a rare complication of metastatic breast cancer (MBC), with high rates of morbidity/mortality. Large cohorts are scarce. Our study aimed to describe the largest-to-date real-life population of MBC patients treated with intrathecal (IT) therapy and to evaluate prognostic models.

Methods

ESME MBC database (NCT03275311) includes all consecutive patients having started treatment for MBC since 2008. Overall survival (OS) of patients treated with IT therapy was estimated using the Kaplan-Meier method. Prognostic models were constructed using Cox proportional hazards models. Performance was evaluated using C-index and calibration plots.

Results

Of 22,266 female patients included in the ESME database covering 2008-2016, 312 were IT-treated with methotrexate, cytarabine or thiotepa and included in our analysis (15 patients have been excluded because of lack of data on the treatment line). Compared with non-IT treated ones, these were younger at MBC relapse (median age 52 years vs 61 years) and had more often lobular histology (23.4% vs 12.7%) or triple-negative subtype (24.7% vs 13.3%) (all p<0.001). Median OS was 4.5 months (95% CI 3.8-5.6) and 1-year survival rate was 25.6%. In case of IT therapy, significant prognostic factors associated with worse outcome by multivariable analysis were triple-negative subtype (HR=1.81 [95%CI 1.32-2.47]), treatment line ≥ 3 (HR=1.88 [95% CI 1.30-2.73]), ≥ 3 other metastatic sites (HR=1.33 [95%CI 1.01-1.74]), and IT cytarabine or thiotepa vs methotrexate (HR=1.68 [95%CI 1.28-2.22]), while concomitant systemic therapy was associated with better OS (HR=0.47 [95%CI 0.35-0.62]) (all p<0.001). We validated two previously published prognostic scores, the Curie score and the breast graded prognostic assessment, both with C-index of 0.57.

Conclusions

MBC patients with LM treated with IT therapy have a poor prognosis. However, in this large series, we could identify a subgroup of patients with better prognosis, when concomitant systemic therapy and IT methotrexate were used.

Clinical trial identification

NCT03275311.

Legal entity responsible for the study

UNICANCER.

Funding

UNICANCER. The ESME MBC database receives financial support from an industrial consortium (Roche, Pfizer, AstraZeneca, MSD, Eisai and Daiichi Sankyo). Data collection, analysis and publication are managed entirely by R&D UNICANCER independently of the industrial consortium.

Disclosure

M. Campone: Honoraria (self): Lilly; Advisory/Consultancy, Speaker Bureau/Expert testimony: Novartis; Advisory/Consultancy: GT1. All other authors have declared no conflicts of interest.

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113P - Efficacy of oral etoposide associated with trastuzumab in HER2-positive metastatic breast cancer: results from the Institut Curie’s database.

Abstract

Background

The TOP2A (encoding topoisomerase II) and HER2 genes are co-amplified in about 40% of HER2 positive (HER2+) breast cancers. The topoisomerase-II inhibitor etoposide (oral VP16) has demonstrated clinical activity in metastatic breast cancer (MBC). However, the clinical benefit of trastuzumab combined with oral VP16 (T-VP16) in HER2+ MBC has not been evaluated.

Methods

Patients treated at Institut Curie Hospitals (Paris and Saint Cloud, France) with T-VP16 for HER2+ MBC were retrieved by an in-silico search. A waiver of informed consent was obtained from the local IRB. Clinical and pathological data were collected by trained medical oncologists. The primary study endpoint was progression-free survival (PFS) assessed by the Kaplan Meier method. Secondary endpoints were: overall survival (OS), long response rate (PFS>6 months), clinical benefit (defined as a PFS than 6 months AND longer than the PFS achieved by the previous line of treatment), response rate, and toxicity.

Results

From 2008 to 2016, 43 patients with HER2+ MBC who received T-VP16 were included. The median number of previous chemotherapy lines was 7 (range 1-13). The median PFS and OS were 2.9 months (95% CI [2.4-4.7]) and 11.3 months (95% CI [8.3-25.0]), respectively. Twelve patients (27.9%) had a long response to treatment including nine (20.9%) with clinical benefit. A complete response was obtained for 3 patients. Only 4 patients stopped treatment for toxicity.

Conclusions

The favorable clinical benefit, good tolerance and low cost suggest that T-VP16 is a relevant option for patients with heavily pretreated HER2-positive MBC. TOP2A and HER2 co-amplification data will be presented at the meeting.

Legal entity responsible for the study

Institut Curie.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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