A Phase II Study of Talimogene Laherparepvec for Patients With Inoperable Locoregional Recurrence of Breast Cancer

Abstract

Purpose: Talimogene laherparepvec (T-VEC) is an immunotherapy that generates local tumor lysis and systemic antitumor immune response. We studied the efficacy of intratumoral administration of T-VEC as monotherapy for inoperable locoregional recurrence of breast cancer.Methods: Patients had to have cutaneous, subcutaneous, or nodal tumors injectable with T-VEC. T-VEC was injected intratumorally at 106 PFU/mL on day 1 (cycle 1), 108 PFU/mL on day 22 (cycle 2), and 108 PFU/mL every 2 weeks thereafter (cycles ≥3). Local lesions were photographed before each cycle.Results: Nine patients were enrolled, 6 with only locoregional disease and 3 with both locoregional and distant disease. No patient completed the planned 10 cycles or achieved complete or partial response. The median number of cycles administered was 4 (range, 3-8). Seven patients withdrew prematurely because of uncontrolled disease progression, 1 withdrew after cycle 3 because of fatigue, and 1 withdrew after cycle 4 for reasons unrelated to study treatment. Median progression-free survival and overall survival were 77 days (95% CI, 63-NA) and 361 days (95% CI, 240-NA). Two patients received 8 cycles with clinically stable disease as the best response. The most common grade 2 or higher adverse event was injection site reaction (n=7, 78%).Conclusion: None of the patients was able to complete the planned 10 cycles due to the disease progression. Future studies could examine whether combining intratumoral T-VEC with concurrent systemic therapy produces better outcomes.Trial registration number and date of registration: ClinicalTrials.gov Identifier: NCT02658812; registered [January 14, 2016]

Looking for biomarkers in interferon response pathway to predict response to oncolytic HSV-1 in breast cancer: An ex vivo study

“…The level of IFNs signaling impairment and the dysregulation of associated genes in the cancer cells of different patients further supports the differences in how each patient responds to virotherapy. Oncolytic virotherapy is an encouraging breast cancer therapy (13)(14)(15) and identi cation of realistic IFN-mediated biomarkers to target patients who are most likely responsive to virotherapy is essential. To study this, we examined the e cacy of a G207-like oHSV-1, named oHSV-RR, to infect the primary tissue culture of breast cancer patients.…”