An open-label, pilot study of veliparib and lapatinib in patients with metastatic, triple-negative breast cancer
| Autor: | Edward P. Acosta, Jori E. May, Lisle Nabell, Eva Olariu, Andres Forero-Torres, Erica Stringer-Reasor, Dongquan Chen, Eddy S. Yang, Valerie Caterinicchia, Gabrielle B. Rocque, Carla I. Falkson, Christos Vaklavas, Deborah L. Della Manna, Yufeng Li |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Oncology
Adult medicine.medical_specialty Synthetic lethality Veliparib medicine.medical_treatment DNA repair Pilot Projects Triple Negative Breast Neoplasms Lapatinib lcsh:RC254-282 Targeted therapy 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Breast cancer Triple-negative breast cancer Internal medicine Antineoplastic Combined Chemotherapy Protocols medicine Humans Neoplasm Metastasis PARP inhibitors 030304 developmental biology Neoplasm Staging 0303 health sciences Taxane business.industry Cancer Disease Management Middle Aged medicine.disease lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens Treatment Outcome Tolerability chemistry 030220 oncology & carcinogenesis Benzimidazoles Female Drug Monitoring business medicine.drug Research Article |
| Zdroj: | Breast Cancer Research, Vol 23, Iss 1, Pp 1-12 (2021) Breast Cancer Research : BCR |
| ISSN: | 0215-8507 |
| Popis: | 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 |
| Databáze: | OpenAIRE |
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