The possibility of aiming at the chronicization of the disease opens up for patients with melanoma, renal and lung cancer. Progress also for that of the esophagus
Change the way you treat certain types of skin melanoma, kidney and lung cancers. Thanks to immunotherapy, and in particular to the combination of different immunotherapeutic molecules, the goal of chronicizing these neoplasms when they arrive at an advanced or metastatic stage is approaching. According to statistics, in fact, thanks to the new treatments available also in Italy 49% of patients with live melanoma at 6 and a half years and 48% of those with renal cell carcinoma survive to five years. In the lung, on the other hand, the risk of death appears to be reduced by 28% with dual immunotherapy combined with low-dose chemotherapy.
Chronic various forms of metastatic cancer
In particular, the Italian Medicines Agency (Aifa) has approved the reimbursement of the combination of two immunoncological molecules, nivolumab and ipilimumab, for the first-line treatment of advanced melanoma; intermediate or poor risk advanced renal cell carcinoma and, in combination with two courses of platinum-based chemotherapy; of metastatic non-small cell lung cancer without EGFR and ALK mutation. Furthermore, Aifa has also given the green light to monotherapy with nivolumab in the second line in esophageal cancer. The combination of nivolumab and ipilimumab allows to obtain a complete and synergistic mechanism of action, because it is directed towards two different proteins that inhibit the activation of the immune system (PD-1 and CTLA-4) – explains Paolo Marchetti, professor of Oncology at the University La Sapienza of Rome and president of the Foundation for personalized medicine -. Thanks to the dual immunotherapy, the possibility of chronicizing many forms of metastatic cancer becomes concrete. The benefits offered by the combination of the two immunoncological molecules consist of faster and more lasting responses and long-term survival, as also highlighted in the meta-analysis, coordinated by the University La Sapienza of Rome and published in the Journal of Translational Medicine, which he considered 7 studies, conducted between 2010 and 2020, on more than 2,420 patients affected by melanoma, small cell and non-small cell lung, bladder, gastric, sarcoma, mesothelioma. The combination of nivolumab and ipilimumab demonstrated agnostic efficacy, i.e. across and beyond cancer type, increasing responses by 68%.
Melanoma, from a few months of life to several years
In 2020, in Italy, they were almost estimated 14,900 new diagnoses of melanoma. This skin cancer represented the ideal model to test the effectiveness of immunoncology – he says Paolo Ascierto, director of the Unit of Oncology, melanoma, oncological immunotherapy and innovative therapies of Pascale in Naples -. Until a few years ago there were no really effective therapies: before the arrival of immunotherapy the life expectancy of patients with metastatic disease was about 6 months and less than 10% were alive at five years. LItaly has made a decisive contribution to the research that made immunoncological therapies available to people affected by very advanced cancer. The Pascale of Naples, with over 4,000 patients treated with immunotherapy since 2010, is among the first centers in the world for the number of treatments. And Campania, on the proposal of Pascale, the only Region in Italy that, since 2019, guarantees the reimbursement of the combination of nivolumab and ipilimumab for all patients affected by melanoma with brain metastases. In the international phase 3 study, CheckMate -067, 49% of patients treated with the nivolumab and ipilimumab first-line combination were alive at 6.5 years. Notably, the median overall survival was 72.1 months, the longest to date reported in a phase three study in advanced melanoma. In addition, dual immunotherapy is effective in the long term, given that 77% of patients alive at 5 years and who received the combination no longer needed to receive systemic treatment, adds Ascierto.
It works even in the most difficult kidney cancer patients
The mix of nivolumab and ipilimumab changes the prospects for treatment in the kidney cancer. In 2020, in Italy, they were estimated 13,500 new cases and more than 144,000 people live after diagnosis. The most frequent form is the clear cell one – he underlines Giuseppe Procopio, Head of Genitourinary Medical Oncology of the IRCCS Foundation National Cancer Institute of Milan -. More than 50% of patients with early stage disease recover, 30% arrive at the diagnosis already at an advanced stage and, in a third of cases the disease can recur in metastatic form after surgery. Historically, 5-year survival in advanced or metastatic disease did not exceed 13%. Today, however, thanks to the combination of nivolumab and ipilimumab at the forefront, 48% live at 5 years, as evidenced by the Phase 3 CheckMate -214 study. According to the expert, the data from the compassionate use program on the combination confirm, in daily clinical practice, the excellent results of the pivotal study: 324 patients with kidney cancer from 86 Italian centers were involved, not usually included in randomized studies, for example elderly people with comorbidities and people in very advanced stages, therefore more difficult to treat, or with particular histological variants of kidney cancer – continues Giuseppe Procopio -. The “real world” program showed, in a heterogeneous and unselected population, that the efficacy and tolerability profile of the combination remained unaltered and in line with what emerged in the pivotal phase three study.
Non-small cell lung cancer
In 2020 in Italy they were almost estimated 41,000 new cases of lung cancer and late-stage diagnoses reach 70%, with few treatment options. In fact, the 5-year survival in metastatic non-small cell lung cancer is around 15%. Hence the importance of Aifa’s decision which makes available a new very effective weapon for clinicians and patients in our country – he explains Cesare Gridelli, director of the Onco-hematology Department of the Moscati Hospital of Avellino -. In the most common form of lung cancer, non-small cell lung cancer, dual immunotherapy with nivolumab plus ipilimumab, combined with limited courses of chemotherapy, ie two instead of the “classic” four, reduces the risk of death by 28% and the risk of disease progression by 33%. In addition, as evidenced in the Phase 3 CheckMate -9LA study, 38% of patients receiving this regimen live at two years, compared with 26% of those treated with chemotherapy alone. Dual immuno-oncological therapy in association with two courses of chemotherapy, at the forefront of metastatic cancer, improves both overall and progression-free survival – continues Cesare Gridelli -. The added benefit of this approach is the use of limited courses of chemotherapy, which allows to reduce side effects. With this scheme, the patient ends chemotherapy in less than a month and continues immunotherapy treatment.
Esophagus, neoplasm too often discovered late
Another neoplasm too often identified in an advanced stage the tumor of the esophagus. In 2020, in Italy, they were estimated 2,400 new cases, constantly increasing. About half diagnosed at an advanced stage, with a strong impact on the patient’s daily life, especially on his ability to eat and drink – remember Stefano Cascinu, director of the Cancer Center IRCCS San Raffaele Hospital in Milan and professor of medical oncology at the Vita-Salute San Raffaele University -. Today, chemotherapy is the standard treatment for these patients, but the prognosis remains poor survival does not exceed 10 months. Hence the importance of identifying new effective and tolerable options. Aifa has established the reimbursement of nivolumab for the treatment of unresectable, relapsed or second-line metastatic advanced esophageal squamous cell carcinoma, i.e. after previous chemotherapy. Nivolumab was the first immunotherapy approved in Europe, in November 2020, in gastroesophageal cancer based on the results of the phase 3 ATTRACTION-3 study, which demonstrated a statistically significant and clinically relevant improvement in overall survival in patients who received nivolumab compared to chemotherapy. The immunotherapy drug reduced the risk of death by 23% compared to chemotherapy alone – concludes Cascinu -. Furthermore, immunotherapy has shown an improvement in the quality of life, a very important aspect in patients who are often fragile and affected by other pathologies. The challenge bring the advantages of immunotherapy also as an adjuvant, that is, in the early phase immediately after surgery. Indeed, the use of nivolumab in the early stages of cancer has the potential to prevent recurrence. As demonstrated by the Phase 3 CheckMate -577 study, adjuvant treatment with nivolumab doubled disease-free survival (22.4 months) compared to placebo (11 months), reducing the risk of relapse or death by 31%.
January 28, 2022 (change January 28, 2022 | 16:41)
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