New Hope Against a Rare but Incurable Eye Cancer

By Dennis Thompson
HealthDay reporter

TUESDAY, April 20, 2021 (HealthDay News) – An advanced investigational drug cuts the risk of death in patients with rare but aggressive eye cancer nearly in half, according to new clinical trial data.

Tebentafusp has now become the first drug to improve the overall survival of patients with uveal melanoma, said Dr. Antoni Ribas, past president of the American Association of Cancer Research (AACR), in a HealthDay Now interview.

“Uveal melanoma is a disease that so far has not received any medical treatment,” said Ribas, director of the tumor immunology program at the Jonsson Comprehensive Cancer Center and the Parker Institute for Cancer Immunotherapy. Center at the University of California at Los Angeles. “Nothing had shown improvement over the past 50 years of clinical research.”

Patients randomly selected to receive tebentafusp had almost half the risk of death than those treated with immunotherapy or chemotherapy, according to results presented at the recent AACR annual meeting.

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Research presented at meetings is generally considered preliminary until it is published in a peer-reviewed journal.

“Tebentafusp halved the relative risk of dying and, therefore, had a great impact on prolonging survival in patients with metastasized uveal melanoma,” said clinical trial researcher Dr Jessica Hassel. She is Associate Professor and Section Head at the Department of Dermatology and at the National Center for Tumor Diseases at University Hospital Heidelberg, Germany. “It is therefore the first drug with a proven survival benefit for patients with uveal melanoma, and this was true even in patients where the melanoma has progressed.

Uveal melanoma is rare overall, but the most common eye cancer in adults, Hassel said. It accounts for about 3% to 5% of all melanomas.

The wall of the eye contains three layers. The outer layer is made up of the “white of the eye,” known as the sclera, with a clear part in the front called the cornea through which light passes. The inner layer has a lining of nerve tissue, called a retina, which senses light and transmits optical information to the brain.

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Between these two elements is a layer called uvea, which is where the colorful iris is located, along with the muscles to help your eye focus and the blood vessels to provide oxygen and nutrition to the people. eye cells.

So far, the prognosis for uveal melanoma has been very poor, with people living on average less than a year after cancer has spread from the eye to other parts of the body, Hassel said.

“When uveal melanoma is diagnosed, it is irradiated or operated on depending on the size of the tumor,” she said. “Half of the patients end up developing metastases, mainly to the liver, and at that point, there is no standard of care available.”

Doctors have tried treating the cancer that has spread to the liver, as well as using strong immune-boosting drugs, but “none of these treatments have shown any overall survival benefit,” Hassel said. .

Tebentafusp is a protein that recognizes two different receptor targets, one found on melanoma cells and the other on carcinogenic T cells produced by the immune system, she said. The drug is administered intravenously once a week.

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“Tebentafusp builds a bridge between the tumor and the immune cells, allowing the immune cells to attack the tumor,” Hassel said. “It binds T cells and activates them to fight ocular melanoma cells.”

This trial tested the potential of tebentafusp as a first-line treatment for eye cancer, enrolling 378 people with metastatic uveal melanoma. The researchers gave the experimental drug to 252 of the patients, while the rest received chemotherapy or immunotherapy.

The estimated one-year overall survival rate of patients who contracted tebentafusp was 73%, compared with 59% among those who received other therapies, the researchers reported. This represents a 49% survival advantage for the new drug.

The disease control rate – the percentage of patients who had a complete or partial response to their treatment, or whose disease stabilized for an extended period – was 46% in tebentafusp patients after 12 weeks. This compared to 27% for those who received chemotherapy or immunotherapy.

Side effects mainly affected the skin during the first cycles of treatment, Hassel said, and in more rare cases, patients suffered from an inflammatory “cytokine storm” due to overstimulation of the immune system. Only 2% of patients stopped treatment because of side effects.

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Based on these results, the U.S. Food and Drug Administration granted tebentafusp the breakthrough therapy designation, according to a press release issued in February by Immunocore, developer of the drug.

This designation is intended to accelerate the development and review of drugs for serious or life-threatening conditions, after early clinical evidence indicated that the drug may be significantly better than available therapies.

Researchers now plan to see if tebentafusp can be used to prevent cancer from recurring in uveal melanoma patients who have gone into remission, Hassel said. They also want to test the drug in combination with other drugs that boost the immune system.

Immunocore funded the clinical trial.

More information

The National Cancer Institute in the United States has more on uveal melanoma.

SOURCES: Jessica Hassel, MD, associate professor and section head, Department of Dermatology and National Center for Tumor Diseases, Heidelberg University Hospital, Germany; Antoni Ribas, MD, PhD, director, Tumor Immunology Program, Jonsson Comprehensive Cancer Center, and director, Parker Institute for Cancer Immunotherapy Center, University of California, Los Angeles; American Association for Cancer Research Annual Meeting, April 9, 2021

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