Twelve weeks of neoadjuvant exposure to talimogene laherparepvec (T-VEC) was associated with few high-grade toxicities and a promising pathological complete tumor-response (pCR) rate, according to research (abstract 9508) presented at the 2018 American Society of Clinical Oncology (ASCO) Annual Meeting, held June 1–5 in Chicago.
The interim analysis of neoadjuvant T-VEC demonstrates impressive clinical response in resectable disease,” commented Joshua M.V. Mammen, MD, PhD, of the University of Kansas in Kansas City in a poster-discussion panel. Mammen was not involved in the study.
However, 11 patients (14.5%) in the T-VEC study arm experienced disease progression before surgery could be performed. That might reflect the “high risk of developing metastases inherent within this study population,” and some of those patients were unlikely to have benefitted from surgery, the study authors argued.
"Observed toxicities were minimal,” Mammen said. “We await results for recurrence-free survival and overall survival.”
There is a need for neoadjuvant treatment options to reduce the high risk of recurrence after the complete resection of stage IIB–IVM1a melanomas, noted lead study author Robert H.I. Andtbacka, MD, of the University of Utah Huntsman Cancer Institute in Salt Lake City, and coauthors.
T-VEC immunotherapy is a genetically engineered oncolytic herpes simplex virus-1 that replicates within tumor cells and releases chemical signals that trigger heightened antitumor immune surveillance and attack. It is injected directly into the tumor and has both local and systemic antitumor effects.
Previous research has suggested that T-VEC might reduce the risk of metastasis in inoperable stage IIIB–IVM1a melanoma, suggesting potential value in the neoadjuvant setting for patients with resectable tumors.
The study authors conducted a randomized, open-label phase II study to evaluate neoadjuvant T-VEC in this patient population. They enrolled 150 adult patients with Eastern Cooperative Oncology Group performance status of 0 or 1 and histologically confirmed stage IIB–IVM1a melanoma and that were eligible for resection (AJCC American Joint Commission on Cancer 7th Edition Cancer Staging Manual), and no ocular or mucosal melanoma. Patients with a history of immunodeficiency-associated melanoma, a history of symptomatic autoimmune disease, or active hepatitis B or C or HIV infection were not eligible for the study.
Patients were randomly assigned to receive either six doses of T-VEC followed by surgery (n = 76) or be treated with surgical resection alone, without T-VEC (n = 74).
However, disease progression was common in the T-VEC group before surgery was scheduled for week 13 to 18, preventing 19 (25%) of patients from undergoing the protocol-defined surgery, compared with 5 patients (6.8%) in the surgery-only group.
Clinical response did not predict pathological complete response (pCR) following neoadjuvant T-VEC; only 3 patients (4%) in the T-VEC group saw a clinical CR, compared with 12 (21%) who had a pCR. “While all patients with a clinical CR achieved pCR, some patients with clinical SD [stable disease] or PD [progressive disease] also achieved pCR,” the authors reported.
Presurgical treatment-emergent adverse events (TEAEs) included influenza-like symptoms (34%), pyrexia (31.5%), fatigue (26%), headache and chills (23% each), arthralgia (12%), myalgia (11%), nausea (11%), diarrhea (11%), and vomiting (9.6%). One patient experienced grade 3 TEAE progression of a necrotic leg ulcer. No treatment-related patient deaths were reported.
The study authors plan to perform an interim analysis of 1-year recurrence-free survival, late in 2018.