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Updated: Nov 15, 2025
Studying Triple Negative Breast Cancer Using Orthotopic Breast Cancer Model
Published on: March 20, 2020
An open-label, pilot study of veliparib and lapatinib in patients with metastatic, triple-negative breast cancer
Erica M Stringer-Reasor1, Jori E May1, Eva Olariu2
1Department of Medicine, Division of Hematology Oncology, University of Alabama at Birmingham, Birmingham, AL, USA.
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.
Insights
This study shows that combining lapatinib and veliparib is safe and effective for treating advanced triple-negative breast cancer (TNBC). Further research is recommended for this dual therapy approach in TNBC patients.
Area of Science:
- Oncology
- Pharmacology
- Genetics
Background:
- Poly (ADP-ribose)-polymerase inhibitors (PARPi) are approved for BRCA-mutated cancers.
- Expanding PARPi utility beyond BRCA mutations is an active research area.
- Preclinical models suggest combined EGFR inhibition and PARPi induce synthetic lethality in triple-negative breast cancer (TNBC).
Purpose of the Study:
- To evaluate the safety and clinical activity of lapatinib plus veliparib in patients with metastatic TNBC.
- To assess objective response rates and pharmacokinetic profiles.
- To explore gene expression changes in relation to treatment response.
Main Methods:
- A first-in-human, pilot study (NCT02158507) was conducted.
- Twenty patients with metastatic TNBC and prior chemotherapy were enrolled.
- Exclusion criteria included germline BRCA1/2 mutations; primary endpoints were safety and tolerability.
Main Results:
- Seventeen patients were evaluable for response.
- Four patients (24%) achieved a partial response, and two (12%) had stable disease.
- The combination therapy demonstrated a manageable safety profile with no dose-limiting toxicities or drug-drug interactions.
Conclusions:
- Lapatinib plus veliparib exhibits a manageable safety profile and promising antitumor activity in advanced TNBC.
- Further investigation into dual therapy with EGFR and PARP inhibition is warranted for TNBC treatment.
- Exploratory analysis indicated lower baseline DNA repair scores and higher immunogenicity in responders.
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