Neoadjuvant talimogene laherparepvec (T-VEC; Imlygic) was found to safely extend recurrence-free survival (RFS) in patients with resectable melanoma, according to 3-year follow-up data from a phase 2 study presented at the 32nd Society of Immunotherapy for Cancer (SITC) annual meeting.1
T-VEC is a viral therapy injected directly into melanoma lesions that has posted impressive results—particularly in the treatment of advanced melanoma—since its FDA approval in 2015. Existing evidence has established T-VEC’s tolerability and low risk for associated toxicities, as well as its potential to prime the immune system, possibly eliciting activity against metastatic lesions.
The findings presented at the SITC conference expand the pool of available data on T-VEC’s efficacy in melanoma while validating the immunotherapy combination as a viable treatment strategy in resectable disease. Data from the trial (ClinicalTrials.gov identifier: NCT02211131) showed that at a median follow-up of 41.3 months, the 3-year Kaplan-Meier RFS estimates were 46.5% with T-VEC and 31.0% with immediate surgical resection alone (HR, 0.67; 80% CI, 0.51-0.88; P =.043). The 3-year overall survival (OS) estimates were 83.2% and 71.6% for the immunotherapy and surgery alone, respectively (HR, 0.54; 80% CI, 0.36-0.83; P =.061). A final analysis will be conducted at 5 years.
“To study this drug in patients who have advanced resectable melanoma is a very appropriate indication,” said Gino K. In, MD, MPH, who is an assistant professor of medicine and dermatology at the Norris Comprehensive Cancer Center at the University of Southern California Keck School of Medicine in Los Angeles, California. “Many patients often do present with recurrent disease that is resectable, and while we know that surgery can help improve outcomes for these patients, we also know that using additional therapies together with surgery can help reduce the chance of further recurrences later down the line,” Dr In added.
The trial specifically compared 6 doses of neoadjuvant T-VEC followed by surgical resection with immediate resection alone. The rationale to test these 2 interventions was based on 2-year primary analysis results demonstrating an improvement in RFS and OS in patients who received T-VEC prior to surgery vs those who had immediate surgery.
The study enrolled patient with stage IIIB, IIIC, or IVM1a melanoma eligible for complete surgical resection. The primary end point was RFS; secondary end points included the Kaplan-Meier estimate of RFS rate at 1 and 2 years and the pathological complete response rate, among others.
“This trial demonstrates that T-VEC is suitable for use in the neoadjuvant setting and another useful tool in the treatment of melanoma,” said Phillip Daschner, MSc, program director in the cancer immunology, hematology, and etiology branch at the National Cancer Institute in Bethesda, Maryland. “Additionally, this is real-world data, so you are going to get patients treated with previous therapies, it gives different information to trials with carefully stratified patient selection,” he added.
One of T-VEC’s proposed mechanisms of action includes activity against not only the primary tumor at the injection site but also metastatic disease, which may manifest through T-VEC’s potentiality to prime a systemic immune response.1
“The correlative science from this study thus far has shown that use of T-VEC increases the presence of infiltrating CD8+ T-cells and also PD-L1 expression at tumor injection sites but, there is no correlative data yet to address whether such changes are seen at other metastatic sites,” Dr In said.
Despite a lack of data to confirm this hypothesis, the promising results indicate that the therapy may be having some effect at sites distant from the primary injection site, according to Dr In.
“The fact that the treatment is given for only 12 weeks and that we are seeing prolonged improvements in relapse-free and event-free survival, even 3 years later, does suggest that the biological effect from T-VEC has in fact led to systemic changes as well,” he said.