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How Effective Is Talimogene Laherparepvec Injection in Metastatic Melanoma?

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Key Points

  • 39% of participants (31 patients) had a complete local response to TVEC therapy, and 18% (14 patients) had a partial response.
  • 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.
  • Side effects were mild and self-limited; the most common side effects were flu-like symptoms in 28% of participants (22 patients). Only five patients stopped treatment for a variety of complications, including cold sores or infection.

Injection of a genetically modified virus that induces the body’s own immune cells to attack metastatic melanoma effectively treated almost 40% of patients with tumors that could not be surgically removed, according to findings published by Louie et al in the Journal of the American College of Surgeons.

“Our findings in the real world mimic what the clinical trials have found,” said corresponding author of the study David W. Ollila, MD, FACS, a general surgical oncologist in the Department of Surgery at the University of North Carolina at Chapel Hill. “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.”

About TVEC

The researchers evaluated 80 adult patients treated with talimogene laherparepvec (TVEC) over a 3-year period ending October 1, 2018. The U.S. Food and Drug Administration approved TVEC in 2015 for the treatment of stage IIIB to advanced stage IV metastatic melanoma. TVEC is a genetically modified herpes virus that contains the stimulatory factor known as granulocyte-macrophage colony-stimulating factor that increases a tumor-specific immune response.

TVEC is injected directly into the skin tumor in the physician’s office or clinic and the patient may leave immediately afterward without the severe side effects of chemotherapy or other cancer drugs that act on the body’s immune system. The stimulatory factor sends a signal to attract white blood cells into the tumor, Dr. Ollila explained, thereby inducing the body’s activated immune system to kill the metastatic melanoma cells.

Study Methods and Results

The researchers reported that 46% of participants (37 patients) had stage IIIB disease, 31% (25) had stage IIIC disease, 1% (1) had clinical stage IIID disease, and 20% (16) had distant metastases at the time of treatment. Patients received a median of five cycles of TVEC. Most study patients—57%—received some form of therapy before enrollment in the study.

The researchers found that 39% of participants (31 patients) had a complete local response to TVEC therapy, and 18% (14 patients) had a partial response. Dr. Ollila 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.

Dr. Ollila noted that these findings surpass those from the clinical trial published in the Journal of Clinical Oncology that led to the approval of TVEC—the overall response rate noted in that trial was 26.4%. However, that trial included a higher percentage of patients with metastatic cancer.

TVEC was also well-tolerated by the study patients, Dr. Ollila said. Side effects were mild and self-limited; the most common side effects were flu-like symptoms in 28% of participants (22 patients. 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.

Next Steps

These study results raise the question of administering TVEC with other anticancer treatments, including drugs that inhibit the growth of other types of skin cancer cells. “Can we now use TVEC in combination with these drugs and drive the response rates even higher?” Dr. Ollila said. “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 coauthors are participating.

Besides chemotherapy, another existing treatment for skin cancer is surgical removal of the tumor, but that too can be problematic, Dr. Ollila said. “We know that surgeons will eventually reach a point where surgical resection is no longer feasible.”

Disclosure: The study authors' full disclosures can be found at journal.acs.org.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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