Genetically-Modified Injectable Therapy Viable in Treating Metastatic Melanoma

Injection with talimogene laherparepvec (TVEC), an FDA-approved genetically modified oncolytic herpes virus, can effectively target and treat unresectable metastatic melanoma, according to a new study.

The study, published in the American College of Surgeons, aimed to determine the efficacy of TVEC in patients with unresectable stage 3B-4 melanoma.

TVEC, sold under the brand name Imlygic (Amgen), is a genetically-modified herpes virus that contains a stimulatory factor called GM-CSF, which increases a tumor-specific immune response. It is administered through direct injection into the skin tumor. TVEC was approved by the FDA in 2015 for the treatment of stage 3B to advanced-stage 4 metastatic melanoma.

For the study, the researchers evaluated 80 adult patients treated with TVEC who had available treatment response data with at least 3-months of follow up. Patients received a median of 5 cycles of TVEC. Of the patients, 24% were treated in the head and neck, 11% in an upper extremity, 15% in the torso, and 50% in a lower extremity. Additionally, 46% of the patients had stage 3B disease, 31% had stage 3C disease, 1% had clinical stage 3D disease, and 20% had cancer that spread to a distant site at the time of treatment. Thirty-four percent of patients did not receive therapy prior to TVEC.

Overall, the study showed that 39% of patients had a complete local response to treatment with TVEC and 18% had a partial response. A higher complete local response rate (68%) was observed in patients with stage 3B disease compared with those with higher-stage disease. With a median follow-up of 9 months, there was a complete local response rate in 39% of patients and a partial response in 18% of patients, according to the study. Of those who responded completely, 37% had no evidence of disease at last follow up and received a median of 6 cycles of therapy.

TVEC therapy was well-tolerated by the study patients, with mild and self-limited adverse effects. The most common adverse effect was flu-like symptoms in 28% of patients.

Corresponding author David W. Ollila, MD, FACS, a general surgical oncologist at the University of North Carolina at Chapel Hill, noted that patients with stage 3B/C or stage M1A metastatic melanoma appeared to benefit more from the therapy than those with higher stage cancers. In the previous clinical trial that led to TVEC’s approval, the overall response rate was 26.4%, which was lower than the overall response rate in this study.

“We reported a complete response rate that was higher than the 2015 clinical trial because the clinical trial included higher-risk patients in whom TVEC may have limited effectiveness,” Dr Ollila said in a press release about the findings.

The researchers concluded that TVEC is a viable, durable treatment option for patients with this disease and that TVEC can also be safely administered across anatomic sites that otherwise are not amenable to other local therapies.

References

Louie RJ, Perez MC, Jajja MR, et al. Real world outcomes of talimogene laherparepvec. Therapy: a mult-institutional experience. Journal of the American College of Surgeons. 2019. https://doi.org/10.1016/j.jamcollsurg.2018.12.027

Study Findings Support Genetically Modified Virus Injection into Tumor as a Valid Treatment for Metastatic Melanoma [news release]. American College of Surgeons. https://www.facs.org/media/press-releases/2019/melanoma012519. Accessed January 25, 2019.