Treating patients first with immunotherapy and then with target therapy has proven to be the best strategy for healing from metastatic melanoma. This is demonstrated by a study coordinated by Paolo Ascierto, director of the Department of Melanoma and Immunotherapy of the Cancer Institute of Naples, whose latest results were presented at the Esmo in Paris, the European medical oncology congress currently underway in Paris. . The Secombit study aims to identify the right sequence of therapies in people with metastatic melanoma who have the BRAF gene mutation. The trial experiments with three options to find the best sequence. The first is the combination of target therapies to continue with the combination of two immuno-oncological molecules, nivolumab and ipilimumab, after disease progression. The second option is dual immunotherapy to continue with the combination of target therapy after progression. Finally, the so-called ‘sandwitch arm’, that is the sequence of target therapies and the combination of the two immunotherapies and, only in case of progression, the continuation with target therapies.
“The second option, which involves starting with the combination of immunotherapies, achieves the best 4-year overall survival, equal to 63%, compared to starting with the target therapy (46%) or with the third option ( 59%). Preliminary data indicate an overall progression-free survival of 55% starting with the combination of nivolumab and ipilimumab compared with 29% with targeted therapy and 54% with the third option. The choice of immunotherapy before target therapy is therefore supported by these data, ”Ascierto explained.
To carry out this study, 209 people from 30 centers in 10 European countries were enrolled. Pascale involved more patients, about 40. The Secombit study also showed for the first time that patients with high Ldh, the enzyme that correlates the burden of disease, or who had many metastases, performed better in the second and third therapeutic option. “In the analysis of biomarkers – continues Ascierto – a correlation was observed between high TMB (tumor mutational burder), the mutation in the JAK gene and low levels of the cytokine interferon gamma with survival”.
A spy tells us if immunotherapy will work
Ascierto’s group of researchers also presented an interesting study in Paris whose protagonists are two proteins, Marco and Oas1. The study involved 23 patients with advanced melanoma. These two proteins, which activate the immune system, could test in advance which patients respond to immunotherapy. “Although the study still needs investigation, the patients we enrolled – explains Mallardo, first signer of the study – have shown surprising changes in the responder and non-responder groups, so we are very confident”.
The scientific director of Pascale, Alfredo Budillon, was present at the Esmo in Paris: “The Cancer Institute of Naples – he says – confirms itself as an international point of reference for the treatment and research on melanoma. Secombit is an international non-profit academic study conceived and coordinated by Pascale and we as an Institute will continue to promote with great commitment this type of independent studies with their translational component with analyzes on biomarkers such as those presented today at Esmo by Ascierto’s group. “.