The data collected in clinical practice are NOT always in agreement with what has been seen during clinical trials. This time, however, yes. The case is that of the use of early phase immunotherapy in patients with resected stage III and IV melanoma, that is, in a phase in which the disease has been completely removed. The study that proves this, which is presented at the congress of the European Society of Medical Oncology (ESMO), ongoing until 21 September, is Italian and is the largest program in the world on the use of early phase immunotherapy in clinical practice. daily treatment of melanoma. The results tell us that at two years, relapse-free survival reached 58% and distant metastasis-free survival in 70% of patients. “The extended access program was activated to allow patients to access immunotherapy with adjuvant nivolumab before the approval of the Italian Medicines Agency (AIFA) in this indication, which took place in December 2019 – explains Paolo Ascierto, Unit Director of Melanoma Oncology, Oncological Immunotherapy and Innovative Therapies of the ‘Pascale’ of Naples.
Patients out of clinical trials
The 611 patients, who had different characteristics than those in the pivotal study because, for example, more frail, elderly or with comorbidities, were in fact enrolled between November 2018 and June 2019. “In patients with stage IIIB or IIIC disease, not undergoing adjuvant therapy after surgical resection, the 5-year relapse rate is high, equal to 71% and 85%. It should also be considered that half of the patients with advanced or metastatic melanoma come directly from stages I and II, the others from stage III after progression. The adjuvant immunotherapy lasts only one year, it increases the possibility of avoiding the recurrence of the disease and, therefore, potentially healing the person ”, underlines the oncologist.
The sequence of therapies
Furthermore, the preliminary results of the SECOMBIT study are presented for the first time at the ESMO Congress, which 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 for finding 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. Data at a median follow up of 32.2 months are available. “The second option, which involves starting with the combination of immunotherapies, achieves the best 3-year overall survival, equal to 62%, compared to starting with the target therapy (54%) or with the third option ( 60%). Preliminary data indicate progression-free survival, three years, of 53% starting with the combination of nivolumab and ipilimumab compared to 41% with molecularly targeted therapy and 54% with the third option, ”says Ascierto. “The choice of immunotherapy before target therapy is therefore supported by these data and the objective response rate, which halves from 45% to 25% when administered in the second line”.
New data on LAG-3
Also presented at ESMO is the update of the RELATIVITY-047 study on the combination of relatlimab and nivolumab at the forefront, with the analysis of the subgroups. “Relatlimab is a new immuno-oncological molecule that inhibits the LAG-3 immune checkpoint – concludes Prof. Ascierto -. The results already illustrated last June at the American congress of medical oncology are confirmed: median progression-free survival reached 10.12 months with the combination compared to 4.63 months with nivolumab monotherapy. And the data already highlighted with nivolumab plus ipilimumab is also confirmed, ie the one relating to the treatment-free interval, much higher with the combination (3.22 months) than with monotherapy (1.41 months) “. Pascale played a central role in the development of relatlimab, launching the world‘s first study on the molecule in 2017 with the involvement of around 200 patients, demonstrating that LAG-3 plays a decisive role in resistance to anti-PD1 drugs such as nivolumab , thus representing a further immune checkpoint used by cancer to circumvent the response to immuno-oncological therapies.
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