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Breast Cancer Research
Published in: Breast Cancer Research 1/2021

01-12-2021 | Breast Cancer | Research article

An open-label, pilot study of veliparib and lapatinib in patients with metastatic, triple-negative breast cancer

Authors: Erica M. Stringer-Reasor, Jori E. May, Eva Olariu, Valerie Caterinicchia, Yufeng Li, Dongquan Chen, Deborah L. Della Manna, Gabrielle B. Rocque, Christos Vaklavas, Carla I. Falkson, Lisle M. Nabell, Edward P. Acosta, Andres Forero-Torres, Eddy S. Yang

Published in: Breast Cancer Research | Issue 1/2021

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Abstract

Background

Poly (ADP-ribose)-polymerase inhibitors (PARPi) have been approved for cancer patients with germline BRCA1/2 (gBRCA1/2) mutations, and efforts to expand the utility of PARPi beyond BRCA1/2 are ongoing. In preclinical models of triple-negative breast cancer (TNBC) with intact DNA repair, we have previously shown an induced synthetic lethality with combined EGFR inhibition and PARPi. Here, we report the safety and clinical activity of lapatinib and veliparib in patients with metastatic TNBC.

Methods

A first-in-human, pilot study of lapatinib and veliparib was conducted in metastatic TNBC (NCT02158507). The primary endpoint was safety and tolerability. Secondary endpoints were objective response rates and pharmacokinetic evaluation. Gene expression analysis of pre-treatment tumor biopsies was performed. Key eligibility included TNBC patients with measurable disease and prior anthracycline-based and taxane chemotherapy. Patients with gBRCA1/2 mutations were excluded.

Results

Twenty patients were enrolled, of which 17 were evaluable for response. The median number of prior therapies in the metastatic setting was 1 (range 0–2). Fifty percent of patients were Caucasian, 45% African–American, and 5% Hispanic. Of evaluable patients, 4 demonstrated a partial response and 2 had stable disease. There were no dose-limiting toxicities. Most AEs were limited to grade 1 or 2 and no drug–drug interactions noted. Exploratory gene expression analysis suggested baseline DNA repair pathway score was lower and baseline immunogenicity was higher in the responders compared to non-responders.

Conclusions

Lapatinib plus veliparib therapy has a manageable safety profile and promising antitumor activity in advanced TNBC. Further investigation of dual therapy with EGFR inhibition and PARP inhibition is needed.

Trial registration

ClinicalTrials.​gov, NCT02158507. Registered on 12 September 2014
Appendix
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Metadata
Title
An open-label, pilot study of veliparib and lapatinib in patients with metastatic, triple-negative breast cancer
Authors
Erica M. Stringer-Reasor
Jori E. May
Eva Olariu
Valerie Caterinicchia
Yufeng Li
Dongquan Chen
Deborah L. Della Manna
Gabrielle B. Rocque
Christos Vaklavas
Carla I. Falkson
Lisle M. Nabell
Edward P. Acosta
Andres Forero-Torres
Eddy S. Yang
Publication date
01-12-2021
Publisher
BioMed Central
Published in
Breast Cancer Research / Issue 1/2021
Electronic ISSN: 1465-542X
DOI
https://doi.org/10.1186/s13058-021-01408-9

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