Melanoma, Italy is in pole position on research and treatment. The vademecum of good prevention

Cases of melanoma have almost doubled in Italy in the last fifteen years: from 7,000 in 2008, we have arrived at around 13,000 today, and the incidence is steadily increasing even among the under-40s. Data that speak volumes about the attention, in terms of both prevention and therapeutic innovation, that needs to be devoted to this aggressive tumour that accounts for 4% of all skin neoplasms but is responsible for 80% of skin cancer deaths. Eight out of ten cases are early stages, curable by surgery, but 2,500 people still die of melanoma every year. A challenge that oncologists all over the world are working on, with Italy at the forefront when it comes to scientific research.

It is no coincidence that the latest developments were presented and discussed at the 15th Melanoma Bridge congress in Naples. The new frontier is immunotherapy based on 'oncolytic' viruses: it works in one third of difficult cases, i.e. in patients with metastatic melanoma who no longer respond to standard immunotherapy. "The mechanism of action of RP1 consists in injecting into the tumour nodule, where possible, a genetically modified herpes simplex virus: inside it has a gene coding for a cytokine, capable of activating the immune system to a greater extent where it is inoculated". The speaker is Paolo Ascierto, president of the Melanoma Foundation and Melanoma Bridge and director of Melanoma Oncology, Cancer Immunotherapy and Innovative Therapies at the Pascale Institute in Naples. 'It was seen that in metastatic patients who had failed a previous therapy,' he explains, 'the injection of RP1 together with the immunotherapy nivolumab gave a 38%-40% response rate, hence tumour reduction with a long survival. Not only is the mass reduced where the virus was injected, but also the metastases'. Data emerged from the Phase 2 Ignyte study, so convincing that in the United States the Food and Drug Administration has awarded RP1 the 'stamp' of Breakthrough Therapy that guarantees a fast track to approval. But we are already beyond that: 'On RP1 plus nivolumab, this time as a first-line option in patients with advanced disease, the Phase 3 study will now begin, in which Italy will also participate with several centres,' explains the oncologist from Campania. 'If the positive results are confirmed, the availability of this therapy for patients will be the next step in Europe and Italy as well.

In our country, meanwhile, since last September the SSN has been reimbursing the new first-line therapy which, according to the Phase 2/3 Relativity-047 study, doubles the survival of patients with unresectable and metastatic melanoma. Hence inoperable. They called it 'dual block' because, in a single administration, the two drugs nivolumab (immunotherapy) and relatlimab (human monoclonal antibody) act on two different blocks of immune system inhibition by tumour cells. "It is a combination that can be administered to Pd-L1-negative patients, with the advantage of lower toxicity compared to another immunotherapy also intended for this type of patient," explains Ascierto. He recalls: 'Thanks to immunotherapy, metastatic melanoma has become increasingly curable, so much so that today more than half of patients are alive ten years after diagnosis. With the nivolumab-relatlimab combination, which has increased median progression-free survival by 25% compared to monotherapy, which was an established standard, we aim to improve these results even further'.

Italy, one of the few countries in the world, will also be authorised to use cycles of immunotherapy in a neoadjuvant function, i.e. in support of the operation required, for example, to remove an armpit metastasis. 'We thus have the possibility of treating earlier stages,' says Ascierto, 'in people who have to undergo surgery: we do cycles of neoadjuvant immunotherapy before the operation and then continue post-operatively with adjuvant treatment. Using immunotherapy when the tumour is in place, before surgery, allows us to better immunise the patient by developing an activated immune system that has a more powerful memory effect than classic treatment'.

The turning point in the history of the disease, along with immunotherapy, which is experiencing disruptive progress, could come from the vaccine for which the last step in trials is underway. "The messenger RNA vaccine for melanoma is now in Phase 3 trials and if the study is positive it will go 'to the pharmacy'. Enrolment has been closed, i.e. the number of target patients has been reached, and now we are waiting for the data, which if all goes well we will have at the beginning of 2027,' Ascierto, head of the team that at Pascale on 26 January 2024 was able to administer the mRNA vaccine to the first patient in Italy.