Immunotherapy Effective in Advanced Injectable Melanoma

Researchers have shown for the first time that an oncolytic immunotherapy can have therapeutic benefit in patients with advanced melanoma, according to the results of a phase III study published in the Journal of Clinical Oncology.

Talimogene laherparepvec (T-VEC) is a herpes simplex virus type 1-derived oncolytic immunotherapy that produces granulocyte macrophage colony-stimulating factor (GM-CSF) to enhance antitumor immune responses. In this phase III trial, patients treated with T-VEC had a higher rate of durable response and a longer overall survival than did patients assigned treatment with subcutaneous GM-CSF.

“T-VEC treatment resulted in long lasting [complete responses], suggesting T-VEC could delay or prevent relapses or preclude progression to later stages of disease,” wrote study author Robert H. I. Andtbacka, MD, of the Huntsman Cancer Institute at the University of Utah, and colleagues. “T-VEC represents a novel potential new treatment option for patients with injectable metastatic melanoma and limited visceral disease.”

The trial included 436 patients with injectable, unresectable advanced melanoma who were randomly assigned 2:1 to intralesional T-VEC or subcutaneous GM-CSF. Patients had a median duration of treatment of 23 weeks for T-VEC and 10 weeks for GM-CSF.

Patients assigned T-VEC had a durable response rate-an objective response lasting 6 months or longer-of 16.3% compared with 2.1% for patients assigned GM-CSF (P < .001). Thirty-two patients in the T-VEC arm had a complete response compared with one patient in the GM-CSF arm. According to the researchers, at the time of final tumor assessment included in the primary analysis of response, 56 of 78 patients assigned T-VEC had ongoing responses.

The median overall survival was also longer among patients assigned T-VEC compared with GM-CSF (23.3 months vs 18.9 months; P = .051).

“T-VEC efficacy was most pronounced in patients with stage IIIB, IIIC, or IVM1a disease and in patients with treatment-naive disease,” the researchers wrote.

Specifically, patients with stage IIIB or IIIC disease had a durable response rate of 33% when assigned T-VEC compared with 0% with GM-CSF, patients with stage IVM1 disease had a response rate of 16% compared with 2%, and patients with treatment-naive disease had a response rate of 24% compared with 0%.

“Although the reasons for the apparent differences in activity by disease stage are not known, it is possible that some patients with visceral disease may have had insufficient survival time to derive benefit from T-VEC–initiated systemic antitumor immunity,” the researchers wrote. “Alternatively, injection of T-VEC into dermal, subcutaneous, and nodal metastases may activate T cells that preferentially traffic to metastases in similar anatomic sites.”

Overall the treatment was well tolerated. The most common adverse events with T-VEC were fatigue, chills, and pyrexia. Grade 3 or 4 cellulitis occurred in 2.1% of patients assigned T-VEC.