Modified herpes virus effective against late-stage melanoma

Healthline/Medical News Today Jan 30, 2019

A new treatment with a genetically modified herpes virus is effective against stage 3B and stage 4 melanoma, a recent human study confirms.

In 2015, the US Food and Drug Administration (FDA) approved the use of talimogene laherparepvec (TVEC) for the treatment of late-stage melanoma that doctors cannot remove through surgery. Doctors deliver TVEC through injections directly into the tumor sites. It is a genetically modified herpes virus that acts by stimulating the body's own immune response against metastatic melanoma.

Recently, a team of researchers from the University of North Carolina at Chapel Hill, NC; the Moffitt Cancer Center in Tampa, FL; and Emory University in Atlanta, GA, studied the effects of TVEC treatment in 80 people with late-stage melanoma who had received this therapy for over 3 years. The researchers' findings—which are due to appear in the Journal of the American College of Surgeons—indicate that almost 40% of the people who received this treatment experienced a successful outcome.

"Our findings in the real world mimic what the clinical trials have found. 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." —Co-author Dr. David Ollila

39% of participants saw a complete response

The researchers worked with a total of 80 adults who received TVEC injections over the course of 3 years for the treatment of late-stage metastatic melanoma. Of the total number of participants, 46% (37 people) had stage 3B cancer, 31% (25 people) had stage 3C cancer, 1% (1 person) had clinical stage 3D cancer, and 20% (16 people) had cancer that had spread to a distant site.

Participants went through a median of five cycles of TVEC, and 57% of these individuals had also received a form of cancer therapy before they joined the current study. At the end of the study, the research team concluded that 39% of the participants (a total of 31 individuals) experienced a complete local response to TVEC, which means that the tumors that received therapy disappeared. A further 18% of participants (14 people) experienced partial disappearance of the tumor following this therapy.

"It's pretty hard to ignore a response rate of 39%," notes Dr. Ollila, adding that participants with stage 3B cancer actually had an even higher rate of complete local response following TVEC therapy, at 68%. Participants with stage 3C disease had 26% complete local response rate, and people with stage 4 cancer had a 6% complete local response rate. At a median follow-up point of 12 months, 59% of the participants with stage 3B cancer did not present any signs of tumor recurrence.

Most effective in stage 3 melanoma

As for side effects, Dr. Ollila and colleagues note that the study participants tolerated TVEC well, and any reactions they experienced were mild. The most common side effects reported by participants were flu-like symptoms, seen in 28% of the participants, or 22 individuals.

Compared with the side effects of other, more aggressive cancer therapies, such as chemotherapy, which can be severe, the side effects of TVEC do not appear to cause the same level of discomfort. Only five of the participants had to stop treatment with TVEC due to the complications, which included cold sores and infections.

The current study reports better success rates than a previous trial conducted in 2015 and this, the researchers believe, is likely because the 2015 trial involved a higher number of people with cancer that had spread remotely to other organs. Thus, Dr. Ollila and team suggest that TVEC may be most effective in the case of people with stage 3B, 3C, or stage M1A metastatic melanoma.

"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," says Dr. Ollila.

'No role for traditional chemo any longer'

Following the current study's results, the investigators are also wondering whether administering it alongside other cancer therapies would increase TVEC's effectiveness.

"Can we now use TVEC in combination with these drugs and drive the response rates even higher?" asks Dr. Ollila. "Could the same principle work in metastatic merkel cell and locally advanced squamous cell carcinoma?" The research team is already trying to find the answer to some of these questions in an ongoing clinical trial.

Finally, the investigators note that TVEC may, in the future, provide doctors with a treatment option that means they do not have to remove tumors in melanoma surgically, so avoiding the set of problems and complications that surgery can bring.

"We know that surgeons will eventually reach a point where surgical resection is no longer feasible," says Dr. Ollila, adding, "It appears that there's no role for traditional chemotherapy any longer for treating this disease."

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