A real-world review of patients with unresectable metastatic melanoma treated with the genetically modified herpes virus talimogene laherparepvec (TVEC), showed the intervention was effective in nearly 40% of the examined patients—a higher success rate than was seen in the approval trials. These findings come from a paper published online ahead of print in Journal of the American College of Surgeons (Jan. 25, 2019).
“Our findings in the real world mimic what the clinical trials have found,” said corresponding author Dr. David W. Ollila, in a press release. “It’s a different world now in metastatic melanoma, because instead of the traditional cytotoxic chemotherapy that not only kills cancer cells but also kills normal cells, we’re stimulating the immune system to attack the cancer cells.”
Dr. Ollila is a general surgical oncologist in the department of surgery, University of North Carolina at Chapel Hill.
Researchers evaluated 80 adult patients treated with an FDA-approved oncolytic herpes virus, over a three-year period ending Oct. 1, 2018. The U.S. Food and Drug Administration (FDA) approved TVEC in 2015 for the treatment of stage IIIB to advanced-stage IV metastatic melanoma.
Of the participants, 37 (46%) had stage IIIB disease, 25 (31%) had stage IIIC disease, one (1%) had clinical stage IIID disease, and 16 (20%) had cancer that spread to a distant site at the time of treatment. Patients received a median of five cycles of TVEC. Most of the study patients—57%—had received some form of therapy before enrollment in the study.
Complete local response to TVEC therapy was seen in 31 patients (39%). Another 14 patients (18%) had partial response.
“It’s pretty hard to ignore a response rate of 39 per cent,” Dr. Ollila said. He noted that patients with stage IIIB disease had an even higher complete local response rate of 68%, compared with those with higher-stage disease: 26% for IIIC, 0% for IIID, and 6% for IV.
At a median follow-up of 12 months, 59% of patients with stage IIIB disease showed no signs of recurrent disease.
These findings surpassed those from the clinical trial that led to the approval of TVEC, Dr. Ollia said, where the overall response rate was 26.4%. However, he noted the approval trial included a higher percentage of patients with cancer that had spread to other organs, including the lungs.
TVEC was also well tolerated by the study patients in these real-world settings, Dr. Ollila said. The side effects were mild and self-limited, with the most common observed being flu-like symptoms in 22 patients (28%). Only five patients stopped treatment for a variety of complications, including cold sores or infection.
One key takeaway from the study was that patients with stage IIIB/C or stage M1A metastatic melanoma may benefit more from the drug than those with higher stage cancers, Dr. Ollila said. “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,” he said.
The findings from this study also raise the possibility of combining TVEC treatment with other anti-cancer interventions, including drugs that inhibit the growth of other types of skin cancer cells, said Dr. Ollila.
“Can we now use TVEC in combination with these drugs and drive the response rates even higher?”
“Could the same principle work in metastatic merkel cell and locally advanced squamous cell carcinoma?” The latter is the focus of an ongoing clinical trial in which Dr. Ollila and his co-authors are participating.
TVEC treatment may also be a tool to use when the limitations of surgical treatments are reached, he said. “We know that surgeons will eventually reach a point where surgical resection is no longer feasible.”