Neoadjuvant T-VEC confers durable survival benefits for resectable melanoma
Click Here to Manage Email Alerts
Key takeaways:
- Patients with resectable melanoma who received T-VEC prior to surgery achieved better 5-year OS than those who underwent surgery alone.
- T-VEC-treated patients also achieved longer recurrence-free survival.
Neoadjuvant talimogene laherparepvec conferred durable benefits for patients with advanced resectable melanoma, according to study results published in JAMA Oncology.
The approach appeared associated with significantly higher rates of OS, RFS and EFS at 5 years.
“The improvement in survival outcomes is likely the result of an induced systemic immunologic antitumor effect, as shown by elevated CD8 density after [talimogene laherparepvec] treatment,” Reinhard Dummer, MD, professor and vice chairman of the department of dermatology at University of Zurich, and colleagues wrote. “These results demonstrate that neoadjuvant T-VEC plus surgery improves cancer-related outcomes vs. surgery alone, with acceptable safety.”
Background and methodology
Patients with advanced melanoma face a high risk for recurrence after surgical resection. Novel approaches, including use of neoadjuvant immunotherapies, have been evaluated as potential strategies to improve outcomes.
Talimogene laherparepvec (Imlygic, Amgen), also called T-VEC, is a modified herpes simplex virus-1-based oncolytic immunotherapy designed to replicate in tumor cells to support recruitment of T cells and natural killer cells.
Dummer and colleagues conducted a randomized phase 2 trial that included 150 patients with resectable stage IIIB to stage IVM1a melanoma and at least one injectable cutaneous, subcutaneous or nodal lesion.
Researchers assigned patients 1:1 to surgery with or without six doses of neoadjuvant T-VEC.
The patients assigned neoadjuvant T-VEC received an intralesional injection at 4 mL of 106 plaque-forming units (PFU)/mL on day 1 of week 1, followed by 4 mL of 108 PFU/mL on day 1 of weeks 4, 6, 8, 10 and 12.
Difference in recurrence-free survival (RFS) in the intention-to-treat population served as the primary endpoint. Secondary endpoints included OS, local RFS, regional RFS and distant metastasis-free survival.
The T-VEC and surgery-alone groups included similar percentages of patients with stage IIIB (36.8% vs. 35.1%), stage IIIC (39.5% vs. 47.3%) and stage IVM1a disease (22.4% vs. 17.6%).
Ten patients (13.7%) assigned T-VEC and 22 patients (31.9% assigned surgery alone received adjuvant therapy.
Median follow-up was 63.3 months (range, 0.1–86.8).
Key findings
Results showed significantly improved outcomes with neoadjuvant T-VEC.
Patients assigned T-VEC achieved higher rates of 5-year RFS (22.3 vs. 15.2%; HR = 0.76; 80% CI, 0.6-0.97), EFS (43.7% vs. 27.4%; HR = 0.57; 80% CI, 0.43-0.76) and OS (77.3% vs. 62.7%; HR = 0.54; 80% CI, 0.36-0.81).
T-VEC also appeared associated with improvements in local RFS (HR = 0.82; 80% CI, 0.64-1.06), regional RFS (HR = 0.81; 80% CI, 0.62-1.05) and distant metastasis-free survival (HR = 0.73; 80% CI, 0.57-0.94).
Researchers acknowledged limitations in trial design, specifically related to the definition and assessment of RFS.
“Neoadjuvant therapy is a rapidly evolving field that has shown early signs of dramatic benefits for patients with advanced resectable melanoma,” Dummer and colleagues wrote. “These results support further investigation of neoadjuvant [talimogene laherparepvec] combined with checkpoint inhibitors for [this patient population].”
Collapse
Read more about
Click Here to Manage Email Alerts