Breast Oncology Department, Moffitt Cancer Center, Tampa, Florida.
Clinical Trials Office, Moffitt Cancer Center, Tampa, Florida.
Clin Cancer Res. 2021 Feb 15;27(4):1012-1018. doi: 10.1158/1078-0432.CCR-20-3105. Epub 2020 Nov 20.
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 with stage II-III TNBC enrolled in a 3+3 phase I trial (NCT02779855) of two TVEC dose levels [DL; DL 1 = 10 plaque-forming units (PFU) × 5 doses; DL 2 = 10 PFUs first dose, then 10 PFUs × 4 doses] on weeks 1, 4, 6, 8, and 10 plus weekly paclitaxel (80 mg/m) for 12 weeks, followed by doxorubicin/cyclophosphamide (60/600 mg/m) 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.
Nine patients [DL 1 ( = 3); DL 2 ( = 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 ( = 8), chills ( = 3), hematomas ( = 3), and injection site pain ( = 3). Thromboembolic events ( = 2) and bradycardia ( = 1) occurred during or after NAC. Five patients (55%) achieved RCB0, 2 had RCB1 (22%), and 2 had RCB2 (22%).
The addition of TVEC to NAC was feasible at the approved dose, with manageable toxicity. The complete response rate was 55%.
替莫唑胺拉帕替尼（TVEC）是一种获批用于治疗黑色素瘤的溶瘤单纯疱疹 1 型病毒。我们假设肿瘤内 TVEC 可能增强新辅助化疗（NAC）的反应。本文报告了一项联合 NAC 和 TVEC 治疗三阴性乳腺癌（TNBC）的试验结果。
入组了 II-III 期 TNBC 患者的一项 3+3 期 I 期试验（NCT02779855），患者接受两个 TVEC 剂量水平 [DL；DL1=10 噬斑形成单位（PFU）×5 剂量；DL2=10PFU 首剂量，然后 10PFU×4 剂量]，于第 1、4、6、8 和 10 周，以及第 12 周每周紫杉醇（80mg/m），随后每 2 周多柔比星/环磷酰胺（60/600mg/m）8 周。术后使用残留肿瘤负担（RCB）进行反应评估。主要终点为安全性和最大耐受剂量（MTD）。次要终点为 RCB0 率和免疫相关性。DLT 规则为 TVEC 引起的第 1-5 周 3-5 级不良事件。
入组了 9 例患者[DL1（=3）；DL2（=6）]。6 例为 II 期疾病，3 例为 III 期（6 例临床 N）。未发生 DLT，MTD 为 DL2。TVEC 最常见的毒性反应为发热（=8）、寒战（=3）、血肿（=3）和注射部位疼痛（=3）。血栓栓塞事件（=2）和心动过缓（=1）发生在 NAC 期间或之后。5 例患者（55%）达到 RCB0，2 例患者达到 RCB1（22%），2 例患者达到 RCB2（22%）。
在批准的剂量下，TVEC 联合 NAC 是可行的，毒性反应可管理。完全缓解率为 55%。
