It WORKS for kidney , lung and head-neck tumors , but there are promising data for bladder , liver and brain . It is the immuno-oncology, the innovative therapeutic approach to which above all it looks like a new effective weapon to fight cancer and lengthen long-term survival, guaranteeing a good quality of life. Immuno-oncology will be one of the central themes of the 52nd Congress of the American Society of Clinical Oncology (ASCO), the most important world oncology appointment held in Chicago until June 7th.

The neoplasms for which it works. So far immuno-oncology has shown important results in , head-neck district and in the lung, one of the most frequent. Promising studies are also underway in bladder, liver and brain cancer.

An ‘immune checkpoint’. “This approach works in kidney cancer, where chemotherapy and radiotherapy have proven to be historically not very effective – explains Sergio Bracarda, Director of the UOC of Medical Oncology of Arezzo, Azienda Usl Toscana Sud Est -. In particular nivolumab is an inhibitor of the immune ‘checkpoint’ PD-1, a molecule involved in the mechanisms that allow the tumor to evade control of the immune system”. Last April, the European regulatory agency (Ema) approved the molecule in patients with previously treated advanced renal cell carcinoma. The phase III study that led to the registration of nivolumab both in the United States and in Europe showed a reduction in the risk of death by 27%, equal to more than 5 months of life longer than the standard of care. The one-year overall survival rate was 76% for nivolumab versus 66% of the comparison arm. This molecule is showing promising results even in bladder cancer, one of the most frequent with 26,000 new diagnoses estimated in Italy in 2015. “Even atezolizumab, an anti-PD-L1 molecule, has just received an initial approval by the regulatory body US for this pathology “.

Lung cancer. Over the past year there has been an important change in the strategy of treating lung cancer, in the so-called ‘non-small cell’ (NSCLC) form in the metastatic phase. “In particular – says Professor Federico Cappuzzo, director of the Medical Oncology of Ravenna – the results of the latest research suggest that it may be possible to avoid chemotherapy with taxotere in the second line (the progression of the disease after a first line of chemotherapy treatment) , in most patients. In these patients, studies conducted in the last year have shown that immunotherapy (with pembrolizumab, nivolumab, atezolizumab) could take the place of treatment with taxotere.

For this type of lung cancer the patient also has the molecular target drugs that are widening the options available to extend the patient’s survival. There are very interesting data with the new tyrosine kinase inhibitors and with the new ALK inhibitors and a series of new biological targets (ROS-1, MET, BRAF) will soon enter clinical practice. “These molecular anomalies – continues Cappuzzo – should be studied in all cancer patients; unfortunately, only a minority of patients are currently being tested for all these biomarkers. In Italy, for example, the rearrangement of ALK is evaluated in only 30% of patients and this means that the remaining 70% is not given the possibility of using a drug that today guarantees a median life span ranging from 4 to 5 years. To understand the importance of these results it is enough to remember that up to a few years ago the life span for these patients ranged from 6 to 9 months “. This happens because often in patients with lung cancer it is difficult to obtain the material to be analyzed with a biopsy; other times there is a fatalistic attitude on the part of the doctor, which leads him to not request the test. ‘Liquid biopsy’ could help overcome this problem, but is currently used only for EGFR analysis and not for all other biomarkers. other times there is a fatalistic attitude on the part of the doctor, which leads him to not request the test. ‘Liquid biopsy’ could help overcome this problem, but is currently used only for EGFR analysis and not for all other biomarkers. other times there is a fatalistic attitude on the part of the doctor, which leads him to not request the test. ‘Liquid biopsy’ could help overcome this problem, but is currently used only for EGFR analysis and not for all other biomarkers.

Skin cancer. Nivolumab was also reimbursable for metastatic melanoma. “Melanoma has been the forerunner of experiments on immuno-oncology. An approach – emphasizes Paolo Ascierto, president of the Melanoma Foundation and director of the Oncology Unit at the ‘Pascale’ in Naples – which has been shown to improve long-term survival in people affected by this advanced skin cancer: 20% of patients are alive at 10 years, in these cases therefore the disease stops or disappears completely. A result never achieved before and in this skin cancer it is now possible to avoid chemotherapy “. The mechanism of action of immuno-oncology has a transversal efficacy, not limited to a single pathology, precisely because it stimulates the immune system reinforcing it in the fight against the disease.

“The studies underlying the approval of nivolumab – concludes Ascierto, the only Italian involved as chairman at one of the plenary sessions of the Asco congress – they showed a one-year survival rate of over 70% in cases of advanced melanoma, with a 58% reduction in the risk of death. As far as nivolumab is concerned, at the moment we have no data at 10 years as for ipilimumab, the first approved immuno-oncological drug. However, in a phase I study, the survival curve of nivolumab showed a percentage of live patients equal to 35% at 5 years which bodes well. “Moreover, recent studies have shown the efficacy of the combination of ipilimumab and nivolumab The association showed a reduction in tumor size and response rates not only greater than the two drugs administered as monotherapy, but also faster and longer-lasting.

Head and neck tumor. Go ahead thanks to immuno-oncology also in the treatment of head and neck tumors. In our country more than 113 thousand people live with this type of cancer, strongly influenced by lifestyles. In fact, at least 75% of cases are caused by cigarette smoking and alcohol. If these neoplasms are detected early on, they have healing rates between 75 and 100%. Unfortunately, most diagnoses occur at an advanced stage, where the prognosis deteriorates drastically with five-year survival rates of around 40%. In a phase III study, nivolumab demonstrated a one-year overall survival rate of 36% versus 16.6% of the comparator arm, which was chemotherapy. That’s why the

Kidney tumor. Studies with nivolumab for the first time showed a survival advantage of more than 5 months, compared to patients treated with traditional drugs. “It is a very important result,” says Professor Sergio Bracarda, Director of the UOC of Medical Oncology of Arezzo, Azienda USL Toscana SUDEST – which reopens the hope of recovering those patients with very unfavorable prognosis, such as the high-grade forms with a sarcomatoid component that before today were practically orphans of any treatment. At the moment we are considering the possibility of combining two different immunotherapeutic treatments, ipilimumab and nivolumab, at dosages completely different from those used in melanoma. “The study was closed in July last year and the results should be available by the end of the year. “It is incredible to see how this can completely change the therapeutic scenario – continues Bracarda – which in the case of renal carcinoma is an integrated treatment. Desperation surgery”, but a planned surgery. Even on the radiotherapy front, we now have modern treatments capable of overcoming the historical radio-resistance of renal carcinoma. For the third time in a few years the therapeutic scenario of renal carcinoma is completely revolutionizing in a positive sense “.

A new revolution.  The first phase was that of the old immunotherapy with interleukin-2 and interferon alpha. The second revolution, occurred 7 years ago, was that of anti-angiogenic drugs (tyrosine kinase inhibitors, TGF inhibitors). “Now this new revolution – concludes the oncologist – with checkpoint inhibitors that integrates but does not replace therapy with these drugs; many anti-angiogens are also immunomodulating and work perfectly in tandem. And we expect a further revolution for the next two years, that of the new monoclonal anti-angiogenic agents; at the moment a study that associates atezolizumab (immunotherapy) with bevacizumab (monoclonal anti-angiogenic) is in progress “.