Precision Medicine Comes to Ocular Oncology | AAO 2023

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Precision medicine will lead to fewer cases of ocular cancers, earlier diagnosis, and more targeted and sight-saving treatments.

Daniel S. Gombos, M.D.

Daniel S. Gombos, M.D.

Ocular cancers will one day have cures, and the key lies with liquid biopsies, Daniel S. Gombos, M.D., said during a session at the annual meeting of the American Academy of Ophthalmology.

Concepts like liquid biopsy — an assessment of circulating biomarkers in the blood — and precision medicine weren’t even conceivable 30 years ago. But now liquid biopsy has become important in oncology for identifying treatments and monitoring response to therapy and disease progression in lung, breast, prostate, colorectal, ovarian, and other solid cancers.

Eye cancers, although rare, have no early symptoms and may be hard to detect. The American Cancer Society estimates that in 2023, there will be about 3,490 new eye cancers, mainly melanomas, with about 430 deaths. If caught cancer early, the five-year survival rate is 85%.

In the future, however, liquid biopsies of the blood and even aqueous fluid will lead to fewer cases of eye cancer, earlier diagnosis, and more targeted and sight-saving treatments, said Gombos, who is professor and chief, section of ophthalmology at MD Anderson Cancer Center.

Precision medicine in ocular oncology is at its infancy, he said. The FDA’s approval of Kimmtrak (tebentafusp-tebn) in January 2022 to treat patients unresectable or metastatic uveal melanoma, a rare melanoma subtype of the eye, is just the beginning of new ways to treat ocular cancers. Kimmtrak is a bispecific antibody that engages the CD3 T cell, which helps the body’s immune to attack the cancer.

Liquid biopsies are already helping oncologists determine the cancer of origin, and this important implications in ocular oncology. Traces of the cancer’s DNA in the blood can give clues about which treatments are most likely to work for that patient.

For example, Gombos cited a patient from his practice who had both cutaneous melanoma and uveal melanoma. Treatment and prognosis are different depending on the primary cancer.

“In this patient's blood was cell free DNA,” he said. “We tested that DNA …. and saw that her mutations were from cutaneous melanoma, and that this lesion in her eyes started in her skin. With targeted therapy, we saw all of her tumors shrink, and the tumor in her eye evaporated.”

Tumor cells are also in aqueous, the clear fluid in the front part of eye, he said, and in the future, this could provide another mechanism for the detection of cancer, stratifying of patients and disease, and early treatment.

“We can look for critical markers to decide if patients already have that threshold of microscopic disease,” Gombos said. “If they do, they can receive neoadjuvant therapy, and we may never see overt metastatic disease. With the right understanding, with the right testing, we can do things we never did before.”

He suggested that with early treatment, there can be an abscopal effort, where local treatment not only shrinks the targeted tumor but also leads to the shrinkage of other tumors within the body. The immune system is thought to play an important role here. “Patients will never develop metastatic disease because we will train the immune system to never have that occur. This is not science fiction; this is science.”

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