Cancers affecting the lungs, brain, pancreas, esophagus and stomach are still among the most difficult to treat today. Often diagnosed late, in many cases they resist therapy, but several experiments open doors
If already today for some types of cancer we can speak of healing or survival rates at 5 and 10 years from diagnosis that are close to 90% (such as, for example, breast and prostate cancers), for others, unfortunately, the prognosis remains very severe. But the research also continues against the most lethal formsas evidenced by the results of some research on the neoplasms they affect lungs, brain, pancreas, esophagus and stomachpresented at the American Society of Clinical Oncology (Asco) conference in Chicago.
Lung, more early stage healings
The one in the lung, of which they are diagnosed over 41,000 new cases every year in our country, it is still the deadliest tumor in Italy today. “During the Asco congress, there is great attention for the very promising results of integrating neoadjuvant immunotherapy treatment (before surgery) in association with chemotherapy in patients with potentially operable disease – underlines Giampaolo Tortora, director of the Medical Oncology and Cancer Center of the Gemelli Polyclinic in Rome -. The updated data of a study published a few months ago and those of a further trial presented in Chicago clearly indicate, and consistently with each other, that it is possible to almost quadruple the probability of complete pathological responses (i.e. absence of neoplastic cells at post histological examination -surgery) with adding immunotherapy to standard chemotherapy“. In the advanced stage of the disease, information on the combination of immunotherapy with different molecular target drugs arrives: both small molecules inhibiting tyrosine kinase, and monoclonal antibodies that inhibit tumor angiogenesis. Furthermore, the benefits obtainable with new molecularly targeted drugs directed against specific alterations (for example the MET exon 14 gene mutation) are illustrated which, although very rare, have a high responsiveness to these drugs which produce a significant clinical benefit for the patient. . «In the same research trend, updates of very important studies are presented in Chicago with drugs directed against other molecular alterations (such as the KRAS mutation and rare alterations of the EGFR gene) – adds the oncologist -. The ultimate goal of these new therapeutic options will be to increase the fraction of patients with early stage disease who can recover and treating all patients for longer and longer periods, thanks to the different treatments available for the different subtypes of lung neoplasms ».
Brain tumors, several promising studies
Brain tumors are rare and very often have a severe prognosis, as they are extremely aggressive and capable of resisting the therapies available to us. They are roughly 6 thousand new cases registered every year in Italy and over 4 thousand annual deaths they cause among adults and children, but the number includes many types of very different neoplasms. “These differences could be the basis of a turning point in the therapeutic field – he explains Enrico Franceschi, director of the oncology of the nervous system at the IRCCS Institute of Neurological Sciences of Bologna -. In recent years we have been progressively better understanding the profound differences that distinguish these diseases and today we finally have the opportunity to study them in a very precise way thanks to analysis of Dna, Rna and of the epigenetic state which are the basis of their clinical behavior “. The importance of these alterations was such that even the new classification of neoplasms of the central nervous system carried out by the World Health Organization (WHO) in 2021 included molecular alterations as fundamental and indispensable elements in the diagnosis. But genetic mutations of the single tumor are also of crucial importance in the identification of new targeted therapies. «Various studies of great importance are illustrated at Asco 2022 – continues Franceschi -. In a large trial on almost 450 patients (Alliance A071102) the efficacy of an inhibitor of the Parp protein (veliparib), involved in DNA repair, was tested: no increase in survival was shown, but a small percentage of patients may benefit from taking these medicines because they may delay resistance to temozolomide chemotherapy. Of great interest are the results (although preliminary, of a phase I / II trial) in which an anti-PD1 immunotherapeutic agent (cemiplimab) was combined with two immunostimulating agents (INO-5401 and INO-9012) capable of “awakening “T lymphocytes in 52 patients with glioblastoma. The outcomes are very promising both for patients with methylated MGMT (who therefore have a better prognosis) and for others. Finally, the results of the use of the combination of BRAF and MEK inhibitors (dabrafenib and trametinib) in pediatric patients with BRAF mutated gliomas are shown to be remarkable effectiveness in reducing the diseasewith response rates exceeding 50% and duration of these responses of almost two years “.
Pancreas, an important first step with immunotherapy
In Italy it affects about every year 13,700 people, most of them between 60 and 80 years old. Aggressive and almost always lethal (5 years after diagnosis only 8% of patients are alive), it remains a difficult enemy to fight also because it is often diagnosed at an advanced stage (but life expectancy increases if a diagnosis is made. early). At the Chicago conference, however, data were presented that give hope for some progress. “A lot of efforts are focused on understanding the mechanisms that make these tumors among the most resistant to immunotherapydue to the hostile microenvironment that is created around the tumor and does not allow immune cells to see and attack it – he explains Giampaolo Tortora -. A study presented in Chicago goes in this direction, which first showed that long-surviving patients actually have 12 times more activated immune T cells and even more antigens in the tumor than the tumors of those who have a shorter survival. On this basis it was then built an mRna vaccine (cevumeran) specific for the neoantigens present in the tumor of some selected patients, which was realized in real time (another extraordinary progress possible thanks to the innovation) and then administered about 9 weeks after the surgery. The vaccine amplified the specific immune T cells that attacked the tumor and produced a benefit in half of the treated patients. Although it is a phase I trial, for now on only 19 patients, this is the beginning of a new way of personalized immunotherapy which, together with other innovative approaches in progress, could bear fruit in the near future also in this tumor so hostile and refractory to immunotherapy ».
Esophagus, important confirmations
Every year in Italy I am 2,400 new cases of esophageal cancer (the incidence is double in males) and five years after diagnosis only 15% of patients are alive. For many years there has been no progress, but between the end of 2021 and the beginning of 2022, immunotherapy established itself as the most effective therapy in this neoplasm. “From Asco 2022 comes the update and confirmation of the data of the preliminary trials – he says Stefano Cascinufull and primary professor of Medical Oncology at the Vita-Salute San Raffaele University of Milan -. Nivolumab used as adjuvant therapy doubled the median time to relapse in radically operated patients, ranging from about 10 months to over 22 months. But it is above all the percentage of patients who have not had a relapse 4 years after surgery that is the most positive: more than 40% in patients treated with nivolumab, compared to just over 20% in patients who received surgery alone. Even in the advanced phase, nivolumab (study Keynote 590), pembrolizumab (Checkmate 648) and tislelizumab may play an important role in combination with first-line chemotherapy (nivolumab and pembrolizumab), or as monotherapy (tislelizumab) in the second line. The possibility of receiving these drugs is eagerly awaited by oncologists and above all obviously by patients “.
Stomach, progress in cancer already at an advanced stage
Even in stomach cancer, after countless failures, there was the first real success in advanced disease. «In the Checkmate 649 study, nivolumab showed, together with chemotherapy, the possibility of significantly improving survival compared to chemotherapy alone – concludes Cascinu -. Two years old 31% of patients were alive receiving nivolumab against 19% of patients treated with chemotherapy alone. These results were obtained in patients who have a marker called PD-L1 equal to or greater than 5, present in at least half of the patients. Also the use of trastuzumab it was a real innovation in this neoplasm, but it only affected 10-15% of patients ».
June 6, 2022 (change June 6, 2022 | 14:08)
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