Cervical, endometrial and urothelial cancers, how immunotherapy changes treatment strategies

Innovation advances. And opportunities to control apparently distant neoplastic diseases are growing. In this sphere, there is the Aifa's OK to extend the reimbursability of pembrolizumab, which can now be used in as many as 28 different therapeutic scenarios

Simplifying as much as possible, thanks to tailor-made drugs, the body's defence system is prompted to react against neoplastic cells on its own. It then rebels against the cancer, enhancing the response. But there is more: the further one goes with research, the more one discovers that immunotherapy of tumours is finding ever greater scope in the treatment of various, even very different forms of cancer. And above all, one realises that this treatment strategy represents a fundamental stage in that virtuous pathway that passes through prevention, screening and, indeed, therapeutic innovation, in a sort of invisible 'fil rouge' linking pathological conditions that are apparently far removed from one another.

Thus, for what has been called the 'fourth leg' of cancer treatment (immunotherapy), along with surgery, chemo and radiotherapy, the prospects for use are broadening. The Italian Medicines Agency (Aifa) has once again given the go-ahead for the reimbursability of pembrolizumab in three new indications, in addition to the current 25. Clinical practice has thus changed in two gynaecological malignancies: in cervical cancer, with the risk of death reduced by 43% in stage III-IVA patients according to the 2014 FIGO classification, and in endometrial cancer, in which the risk of disease progression has decreased by 66%. Not only that. An additional indication is the treatment of unresectable or metastatic urothelial carcinoma (the urothelium is the inner lining of the bladder - 90% of total cancer cases - renal pelvis, ureters and urethra) in which the risk of death was reduced by 49% and median overall survival more than doubled compared to chemotherapy.

In 2024, in Italia, almost 2,400 new diagnoses of cervical cancer, almost all of which is linked to Hpv or human papilloma virus infection, are estimated. In this sense, the reimbursability of pembrolizumab in combination with chemoradiation therapy (external beam radiotherapy followed by brachytherapy) in specific patients appears to be a fundamental step forward. "For the first time in 25 years, clinical practice is changing in locally advanced high-risk cervical cancer, in which the standard of care until now has been represented by concomitant chemoradiation therapy alone," reports Domenica Lorusso, Head of the Centre for Gynecological Oncology at Humanitas San Pio X and Full Professor of Obstetrics and Gynecology at Humanitas University. "The combination of pembrolizumab with exclusive concomitant chemoradiation therapy increases overall survival in a statistically significant and clinically relevant way.

Not only that: as shown by the results of the KEYNOTE-A18 study published in The Lancet in patients with stage III-IVA cervical cancer (according to the above classification) the combination reduced the risk of both progression and death by 43% compared to chemoradiation therapy alone. 'This is a potentially curative setting,' Lorusso emphasises. The addition of pembrolizumab immunotherapy to chemoradiation therapy will allow more patients to be potentially cured. With this approach, it is possible to add the long-term benefits of immunotherapy with the immediate efficacy of chemoradiation therapy, which have already demonstrated in other diseases a mutually enhancing effect when administered together'.