The history of immunotherapy, as with many innovative anti-cancer approaches, started from those cases where the treatments of the time could no longer do. Over time, however, thanks to the extraordinary success obtained for various cancers in the metastatic phase, oncologists have begun to experiment with immunotherapy not only in the most advanced stages of the disease but also as an adjuvant therapy, i.e. those treatments that are administered to prevent the disease come back. Experiments with growing success as evidenced by the data presented at the main world congresses in the sector, most recently the ASCO – the meeting of the American Society of Clinical Oncology -, the main world event dedicated to the fight against cancer.
Chronic the tumor thanks to immunotherapy
It is a fact that immunotherapy has revolutionized the treatment of many metastatic cancers. Tumors such as melanoma and lung cancer, before the advent of immunotherapists, left no way out. “The turning point – explains Professor Michele Maio, director of the Immuno-Oncology Center at the Policlinico Le Scotte hospital in Siena and president of the NIBIT Foundation – came when we began to look at the fight against cancer by shifting our attention to immune system. Obviously the main goal is to be able to intercept the disease at an early stage, being able to remove it surgically before it metastasizes. When this does not happen, however, we have many weapons at our disposal and that of immunotherapy is certainly the most sophisticated and increasingly effective “.
The basic idea is to exploit the ability of the cells that defend us to recognize and eliminate cancerous cells. In particular, with immunotherapy this capacity is always kept on, which, over time, without any intervention tends to diminish as it is turned off by the tumor itself. “If with melanoma, by combining several drugs, we can reach a survival rate of 50% 5 years after diagnosis, for lung cancer the road is close: in cases of advanced stage disease with chemotherapy only 5% of patients were alive 5 years after diagnosis. With immunotherapy, in a particular population of people that express the PD-L1 receptor, we are at 30%. A way towards the chronicity of cancer ”explains Maio.
Prevent the tumor from coming back
But precisely due to the great ability of immunotherapy to keep the disease under control (now more and more neoplasms are treated on the front line with these drugs), research has been proceeding for some time in an attempt to explore new uses of immunotherapy. “If before we used immunotherapy in the most advanced stages of the disease, today – continues the expert – the data tell us that this strategy can also be useful as an adjuvant, or to avoid relapses of the disease”. And as it was in the first cases, melanoma has again confirmed itself as the pioneering tumor of the adjuvant approach to immunotherapy.
For example, in resected stage III and IV melanomas, i.e. in a phase in which the disease has been completely removed, the 5-year relapse rate is high, equal to 71% and 85%. Being able to count on an adjuvant therapy that lowers these percentages is of fundamental importance. After a few years of experimentation, immunotherapy has also proved effective in these patients. To date, in Italy, both nivolumab and pembrolizumab (drugs also used in the treatment of metastatic melanoma) are approved for use as an adjuvant because they have been shown to be able to significantly reduce these percentages.
The case of kidney cancer. But not only
Important findings that are now starting to be replicated in other cancers. An example is clear cell renal cell carcinoma, a particular form of kidney cancer that does not offer adequate treatment in the case of recurrence. Data from the KEYNOTE-564 study were presented at the ASCO congress in which the use of pembrolizumab has been shown to significantly lower the risk of relapse and significantly increase disease-free survival. A result that, according to ASCO’s Chief Medical Officer, Julie R. Gralow, will represent the new standard of care. Trials, those in adjuvant, which do not stop only at kidney cancer but – as evidenced by the numerous studies presented at ASCO – are also concentrating on lung cancer, head-neck and stomach cancers.
Kidney cancer, the first early stage immunotherapy
by Tiziana Moriconi
Combinations and sequences
Therefore, according to what emerges immunotherapy, whether for the metastatic phase or in the adjuvant strategy, it is becoming more and more a useful strategy in the fight against the chronicity of cancer. “But the challenges are by no means over. First of all, it is necessary to continue studying to better understand which patients respond best to these treatments and which ones do not. Doing so is important because knowing the mechanisms underlying the failure of immunotherapy we can act on them to ensure that the person benefits. But the other big challenge is to improve the efficiency of immunotherapy. Experimenting with different immunotherapeutic sequences and molecules capable of leading the way in immunotherapy is what the scientific community is working on to make tumors more and more curable ”concludes Maio.