A Phase I Trial of Talimogene Laherparepvec in Combination with Neoadjuvant Chemotherapy for the Treatment of Nonmetastatic Triple-Negative Breast Cancer.
Clin Cancer Res
; 27(4): 1012-1018, 2021 02 15.
Article
in En
| MEDLINE
| ID: mdl-33219014
ABSTRACT
PURPOSE:
Talimogene laherparepvec (TVEC) is an oncolytic herpes simplex 1 virus approved for treatment of melanoma. We hypothesized intratumoral TVEC may enhance response to neoadjuvant chemotherapy (NAC). This article reports the results of a trial combining NAC with TVEC for triple-negative breast cancer (TNBC). PATIENTS ANDMETHODS:
Patients with stage II-III TNBC enrolled in a 3+3 phase I trial (NCT02779855) of two TVEC dose levels [DL; DL 1 = 106 plaque-forming units (PFU) × 5 doses; DL 2 = 106 PFUs first dose, then 108 PFUs × 4 doses] on weeks 1, 4, 6, 8, and 10 plus weekly paclitaxel (80 mg/m2) for 12 weeks, followed by doxorubicin/cyclophosphamide (60/600 mg/m2) every 2 weeks for 8 weeks. Postoperative response assessment using residual cancer burden (RCB) was performed. Primary endpoints were safety and MTD. Secondary endpoints were RCB0 rate and immune correlates. Dose-limiting toxicity (DLT) rule was grade 3-5 adverse events due to TVEC during first 5 weeks.RESULTS:
Nine patients [DL 1 (n = 3); DL 2 (n = 6)] were enrolled. Six had stage II disease, and 3 had stage III (6 clinically N+). No DLTs occurred, and MTD was DL 2. Most common toxicities with TVEC were fever (n = 8), chills (n = 3), hematomas (n = 3), and injection site pain (n = 3). Thromboembolic events (n = 2) and bradycardia (n = 1) occurred during or after NAC. Five patients (55%) achieved RCB0, 2 had RCB1 (22%), and 2 had RCB2 (22%).CONCLUSIONS:
The addition of TVEC to NAC was feasible at the approved dose, with manageable toxicity. The complete response rate was 55%.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Biological Products
/
Antineoplastic Combined Chemotherapy Protocols
/
Neoadjuvant Therapy
/
Oncolytic Virotherapy
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Triple Negative Breast Neoplasms
Type of study:
Diagnostic_studies
Limits:
Adult
/
Female
/
Humans
/
Middle aged
Language:
En
Journal:
Clin Cancer Res
Journal subject:
NEOPLASIAS
Year:
2021
Document type:
Article