Researchers led by UNC Lineberger’s David Ollila, MD, FACS, the James H. and Jesse E. Millis Distinguished Professor in the UNC School of Medicine Division of Surgical Oncology, reviewed the results for 80 adult metastatic melanoma patients treated with talimogene laherparepvec, or TVEC.
Injection of TVEC effectively treated almost 40 percent of patients with tumors that could not be surgically removed, researchers reported in the review published in the Journal of the American College of Surgeons.
“Our findings in the real world mimic what the clinical trials have found,” said Ollila, who is a UNC Lineberger member, co-director of the UNC Skin Cancer and Melanoma Program, and surgical oncologist at the UNC Breast Center, in a news release from the American College of Surgeons. “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.”
In addition to Ollila, UNC Lineberger’s Frances Collichio, MD, professor in the UNC School of Medicine Division of Hematology/Oncology, was a study co-author, along with Raphael Louie, MD, a surgical oncology fellow in the UNC School of Medicine Department of Surgery.
The researchers evaluated 80 adult patients treated at three different treatment centers across a three-year period ending Oct. 1 with TVEC, which is sold under the brand name Imlygic by AMGEN Inc. 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 GM-CSF that increases a tumor-specific immune response. TVEC is injected directly into the skin tumor. In the study, patients received a median of five cycles of TVEC. Most study patients, or 57 percent, received some form of therapy before enrollment.
The researchers found that 39 percent of participants, or 31 patients, had a complete local response to TVEC therapy, and 18 percent, or 14 patients, had a partial response.
“It’s pretty hard to ignore a response rate of 39 percent,” Ollila said. He noted that patients with stage IIIB disease had an even higher complete local response rate of 68 percent, compared with those with higher-stage disease: 26 percent for IIIC, zero for IIID, and six percent for IV. At a median follow-up of 12 months, 59 percent of patients with stage IIIB disease showed no signs of recurrent disease.
TVEC was also well tolerated, Ollila said. Side effects were mild and self-limited; the most common side effects were flu-like symptoms in 28 percent of participants, or 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, 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.
Based on these study results, the investigator are now asking whether there is any clinical benefit in administering TVEC with other anti-cancer 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?” 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 Ollila and his co-authors are participating.
Besides chemotherapy, another existing treatment for skin cancer is surgical removal of the tumor, but that too can be problematic, Ollila said.
“We know that surgeons will eventually reach a point where surgical resection is no longer feasible.” The most compelling finding of the study is that it supports TVEC injection as an option for melanoma. “It appears that there’s no role for traditional chemotherapy any longer for treating this disease,” he added.
Jonathan S. Zager, MD, FACS, of Moffitt Cancer Center, Tampa, Florida, and Keith A. Delman, MD, FACS, of Emory University School of Medicine, Atlanta, directed the study at their centers and are lead coauthors with Ollila.
The paper’s other authors are Raphael J. Louie, MD, of the department of surgery, and Frances Collichio, MD, of the department of medicine, at UNC; Matthew C. Perez, MD, Amod A. Sarnaik, MD, FACS, and James Sun, MD, of Moffitt Cancer Center; and Mohammad Raheel Jajja, MD, and Michael Lowe, MD, FACS, of Emory University.
Zager disclosed relationships with Amgen, Array BioPharma, Merck, Delcath Systems, Philogen, Castle Biosciences and Provectus Biopharmaceuticals; Collichio disclosed relationships with Amgen and Novartis; Perez disclosed a relationship with Amgen; and Sarniak disclosed relationships with Iovance Biotherapeutics, B4CC Inc., and Provectus. Ollila and the other study co-authors have no relevant relationships to disclose.