New treatments changing tumour treatment landscape

Potentially groundbreaking new treatments for uveal melanoma, retinoblastoma and melanocytic lesions were among the noteworthy recent developments highlighted in the EURETINA session on tumours.

Chaired by Jens Folke Kiilgaard and Heinrich Heimann, delegates were brought up to date on some of the exciting drugs and new techniques emerging from clinical trials to help manage difficult and complex cases of ocular tumours.

Uveal Melanoma

Heinrich Heimann MD opened the session with an update on tebentafusp, a new FDA approved treatment for uveal melanoma, the most common intraocular cancer in adults representing approximately 3 to 5% of all melanomas. Although rare, metastatic disease develops in approximately 50% of patients and is associated with poor survival due to the lack of effective treatment options. Dr Heimann explained that tebentafusp is a bispecific fusion which works by helping immune cells get close enough to cancer cells to attack them. The FDA clinical trial evaluated the drug as an initial treatment for people with metastatic uveal melanoma. In the trial, 378 patients with previously untreated metastatic uveal melanoma were randomly assigned to receive tebentafusp or one of three established therapies that their doctors could select. The three options for patients in the comparison, or control, group included two immune checkpoint inhibitors and a chemotherapy drug. The overall survival at 1 year was 73% in the tebentafusp group and 59% in the control group. Progression-free survival was also significantly higher in the tebentafusp group than in the control group (31% versus 19% at 6 months). The most common treatment-related adverse events in the tebentafusp group were cytokine-mediated events and skin-related events, including rash (83%), pyrexia (76%), and pruritus (69%).

“This is the first time that such survival rates have been documented with this new kind of drug. Although some people might say that it is not a massive difference, it is a first really big step forward in the treatment of metastatic uveal melanoma,” said Dr Heimann.

Retinoblastoma

Francis Munier MD provided an update on recent progress in the diagnosis and management of retinoblastoma with a particular focus on the benefits of intracameral chemotherapy (ICC). Since retinoblastoma is lethal by metastasis if left untreated, Dr Munier noted that the primary goal of therapy is to preserve life, with ocular survival, visual preservation and quality of life as secondary aims. Although the presence of primary or secondary aqueous seeding in retinoblastoma usually represents a universal indication for enucleation, Dr Munier reported the groundbreaking results obtained in Lausanne using ICC. In a retrospective review of all consecutive patients with primary or secondary spontaneous aqueous seeding treated by a mean of five injections between 2011 and 2021, the overall eye preservation rate was 85% and useful to near-normal visual acuity was reported in 82%. The mean survival follow-up was 49 months (all metastasis free) with a mean event-free follow-up of 40 months for any intraocular retinoblastoma. “Conditional indications to conservative management of anterior segment invasion are now available. Intracameral chemotherapy is safe and efficient to control aqueous seeding with non-sight-threatening toxicity,” he concluded.

Melanocytic Lesions

Martine Jager MD, PhD, discussed new developments in the treatment of melanocytic lesions, focusing on the new drug belzupacap sarotalocan (AU011). She explained that belzupacap sarotalocan consists of a virus-like particle conjugated with an anti-cancer agent to selectively target and destroy cancer cells and activate the immune system with the potential to create long-lasting anti-tumour immunity. The drug is currently in development for ocular cancers, with an ongoing phase 2 dose escalation clinical trial evaluating first-line treatment of choroidal melanoma, a vision- and life-threatening form of eye cancer where standard of care with radiotherapy leaves patients with severe comorbidities, including major vision loss. Dr Jager said that the drug has demonstrated safety and early efficacy in the phase 1b/2 study for choroidal melanoma. In terms of potential treatment for choroidal metastasis, the drug has also shown dose-dependent activity in vivo using mouse models for cancer types known to metastasize to the choroid.

“The study results support further evaluation of belzupacap sarotalocan as a potential treatment for ocular cancers,” she said.

Masquerade Syndromes

Jens Folke Kiilgaard MD concluded the symposium with a look at masquerade syndromes in ocular oncology. He noted that intraocular tumours are often mistaken for a wide range of inflammatory processes or other disease entities, and said that caution should be the watchword of any treating physician when diagnosing such cases.

“If things don’t add up, be careful. For instance, if you have a longstanding uveitis that does not resolve over time or you have a condition that does not really correspond to what is written in the textbook, exercise caution and if you are in doubt refer the patient to the local oncology centre in order to seek help. Always think in terms of potential malignancy, and if in doubt refer to a specialist,” he said.

All registered attendees will be able to view the winning videos via playback on the virtual platform.