Today, when there are so many different therapies for tumors, one of the most important challenges is understanding the sequence in which to use them. And in the case of metastatic melanoma with a Braf gene mutation, there are essentially three possibilities: start with immunotherapy, or with target therapy or apply the so-called “sandwich” strategy, which involves the sequence of target therapies (encorafenib and binimetinib) and the combination of dual immunotherapy (nivolumab and ipilimumab) and, only in case of progression, continuation with targeted therapy. Precisely to understand which was the best, the Secombit study began 5 years ago, coordinated by Paolo Asciertodirector of the Department of Melanoma and Immunotherapy of the Pascale Tumor Institute of Naples, whose latest results were presented today during the Esmo (European Society of Oncology) Congress in Madrid.
Melanoma, how immunotherapy affects brain metastases by Elisa Manacorda 21 October 2023
Three strategies compared
The study compared survival and onset of brain metastases in three groups: group A (target therapy followed by immunotherapy), group B (immunotherapy followed by target therapy) and group C (‘sandwich’ strategy). “Five years after the start of the Secombit study, patients achieved an overall survival of 57% in the sandwich arm and 52% in arm B, and a disease-free survival of 50% – explains Ascierto – Instead, in patients who started with targeted therapy and were then treated with immunotherapy following progression, we observed an overall survival of 45% and a disease-free survival of 27%”.
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The risk of brain metastases
But for the expert the most important data presented at ESMO is the progression free from brain metastases: “Starting treatment with immunotherapy seems to protect against the onset of brain metastases. In fact, at 5 years, in the two arms where immunotherapy was started first, survival free from brain metastases was 85% (sandwich) and 80% (arm B), while in patients who started target in the front line (arm A) it was 57%, i.e. approximately 30% less”. Furthermore, from the analysis of biomarkers, it was observed that the rate of onset of brain metastases is reduced in patients with tumors with a very high mutational load and in patients with inactivating mutations of the JAK (cellular growth factor) molecule.
Epigenetic drugs and immunotherapy against metastatic melanoma by Dario Rubino 10 October 2023
Analyze the NLR marker to understand the tumor
Another study, coordinated by Domenico Mallardo and the group of young Pascale researchers led by Ascierto and also presented at Esmo, then investigated the genetic profile of 78 patients with metastatic melanoma treated on the front line with immunotherapy: the data confirm the role of a biomarker called NLR in predicting prognosis. This acronym – NLR – indicates the ratio between the number of neutrophils and the number of lymphocytes, two different types of immune system cells present in the blood. Well, a greater number of neutrophils compared to lymphocytes is mainly related to genes involved in immunosuppressive, inflammatory and pro-tumor activities.
Thus the microbiota reveals tumors and enhances immunotherapy. The Italian discovery by Tiziana Moriconi 21 September 2023 Topics