ROMA (ITALPRESS) – In the last 10 years, in Italy, cancer deaths have decreased by 9%. An important result, to which the prevention campaigns, the adherence to screening and therapeutic innovation also represented by immunology, which today marks a further change of paradigm. The Italian Pharmaco Agency (AIFA) has approved the repayment of pembrolizumab in 3 new indications, which are added to the current 25. This changes clinical practice in two gynecological neoplasms: in uterine cervix cancer, where death risk was reduced by 43% in III-VAT patients according to FIGO 2014, and in endometrium carcinoma, where the risk of progression of the disease decreased by 66%. To which the urothelial carcinoma is added, unresectable or metastatic, where the risk of death has been reduced by 49% and the overall median survival is more than doubled than chemotherapy. In addition, AIFA recognised the important requirement for therapeutic innovation to the two new regimes based on immunotherapy with pembrolizumab in endometrium and urothelium tumors. These steps forward in the treatment of the three neoplasms are deepened today in Rome, in a press conference promoted by MSD.In 2024, in Italy, almost 2,400 new tumor diagnosis of the uterine cervix was estimated. In almost all cases, this neoplasia is caused by human Papillomavirus infection (HPV), which is transmitted mainly by sexual means. AIFA has approved the repayment of pembrolizumab, in association with chemioradiotherapy (radiotherapy to external bundles followed by brachiterapia), in the treatment of the locally advanced cervix carcinoma in stage III-IVA (according to the classification FIGO 2014) in patients who have not received a definitive therapy. “For the first time in 25 years, clinical practice changes in the tumor of locally advanced uterine cervix at high risk, in which the standard of treatment so far has been represented by the only concomitant chemioradiotherapy – says Sunday Lorusso, Head of the Center of Oncological Gynaecology of Humanitas San Pio X and Professor of Ostetricia and Ginecology of Humanitas University -. The combination of pembrolizumab with exclusive concomitant chemioradiotherapy increases, statistically significant and clinically relevant, global survival.” In particular, in the KEYNOTE-A18 study, published on “The Lancet”, the association reduced the risk of death by 33% compared to the only concomitant chemioradiotherapy and the overall survival rate at 36 months was 82.6% for the association compared to 74.8% of the only chemioradiotherapy in the whole population. Moreover, in the setting of patients in stage III-VAT according to the FIGO classification 2014 the association has reduced the risk of both progression and death of 43% regarding chemioradiotherapy alone. “This is a potentially curative setting – says Professor Lorusso, who is Principal Investigator of the KEYNOTE-A18 studio. For this reason, the addition of immunotherapy with pembrolizumab to chemioradiotherapy will lead to a potential healing a greater number of patients. With this approach, it is possible to sum up the long-term benefits of immunotherapy with the immediate effectiveness of chemioradiotherapy that have already demonstrated in other diseases an effect of mutual strengthening when administered together.” Steps forward also in another gynecological neoplasia, the tumor of the endometrium, which recorded in Italy about 8,650 new diagnosis in 2024. AIFA approved the repayment of pembrolizumab, in association with chemotherapy (carboplatin and paclitaxel), in the treatment of first line of patients suffering from carcinoma of the advanced or recurrent primary endometrium with m system deficitismatch repair (dMMR) and are candidates for systemic therapy. In the study KEYNOTE-868, plus carboplatin and paclitaxel followed by pembrolizumab in monotherapy reduced the risk of progression of disease or death of 66% in patients with mismatch repair deficit, compared to placebo with chemotherapy (carbotin and paclitaxel) followed by only placebo. “The endometrium carcinoma is one of the most frequent female tumors and is the only, among the gynecological neoplasms, with increasing incidence and mortality – says Professor Lorusso. Unfortunately, median survival for patients with recurring or advanced disease does not exceed 36 months. Molecular characterization is crucial and has an impact on therapeutic choice. About 30% of patients have a mismatch repair deficiency tumor, i.e. a malfunction of the DNA repair mechanism. Adding pembrolizumab to chemotherapy is a new first-line therapeutic option for women with advanced or recurrent primary endometrial carcinoma with mismatch repair system deficit, demonstrating a really significant improvement in progression-free survival. This is an extraordinary result.” After decades, the treatment of non-resectable or metastatic urothelial carcinoma also changes, thanks to AIFA’s approval of pembrolizumab refundable, in association with enfortumab Vedotin, a drug-conjugated antibody. In the KEYNOTE-A39 study, published in the “New England Journal of Medicine”, the new association was compared with platinum-based chemotherapy, considered for decades standard treatment, demonstrating a significant and clinically relevant benefit both in terms of progression-free survival and global survival. At a subsequent median follow-up of 29.1 months, the association continued to demonstrate its effectiveness, reducing the risk of death of 49%, with an increase in global median survival more than doubled than chemotherapy. The average duration of the response was 23.3 months for the association and 7 months for chemotherapy. In 2024, in Italy, some 31,000 new cases of bladder cancer were estimated, of which more than 90% were urothelial carcinomas. “Since the 1980s, platinum-based chemotherapy schemes have represented the standard of treatment of unresectable or metastatic urothelial carcinoma – explains Roberto Iacovelli, Associate Professor of Medical Oncology at the Catholic University of the Sacred Heart – University Polyclinic Agostino Gemelli IRCCS in Rome -. The new association, for the first time, has improved survival and control of disease. We are faced with a real revolution of care and a decisive innovation for patients, both for the results obtained and for the nature of treatments.” “Pembrolizumab had already proven to be effective as second-line therapy in urothelial cancer – Professor Iacovelli continues –. On the first line, the pembrolizumab association plus enfortumab Vedotin is characterized by a synergy in the control of the disease to the full advantage of the patients. The disease is thus contrasted on two fronts. One consists of the immune system that is reactivated against the tumor thanks to pembrolizumab, the other is the greater selectivity in the aggression of the sick cells, thanks to the drug-conjugated antibody, which constitutes a more evolved form of chemotherapy. In this way, you get a more lasting and deeper control of neoplasia. Global median survival is more than doubled and the effectiveness of therapy in significantly reducing the extent of the disease is possible in a significant percentage of patients, or 67% compared to 44% of chemotherapy. Since these results have changed the natural history ofthe disease will also change the current clinical practice by overcoming the old chemotherapy standard. In addition, the decision of AIFA is in line with the guidelines of the European Society of Medical Oncology, which recommend this association as a first-line treatment to be preferred in patients with advanced urothelial cancer.” “The MSD immunotherapy with pembrolizumab has marked a quantum leap in oncology, a real paradigm shift that has opened unimaginable roads – concludes Nicoletta Luppi, President and CEO Delegata MSD Italia -. AIFA’s triple widening of indication demonstrates the continuous value of immunotherapy in transforming clinical practice, offering new therapeutic perspectives to cancer patients. A result that arises from a long-term vision and a constant and unequal commitment in Research, supported by one of the broadest clinical development programs in oncology: a diversified pipeline that includes over 25 innovative mechanisms and more than 30 types of cancer. It is this trust in Science, together with the ability to look far away, to allow us to imagine a future in which to continue to offer, to an increasing number of people, more time and more life”.
– photo mec/Italpress –
(ITALPRESS).
