Tumours: immunotherapy is increasingly less burdensome for the patient and the hospital

Time, it is known, is an important variable for those dealing with cancer. Being able to save tens of minutes when carrying out a therapy, simply by changing the route of administration of the drug without affecting its efficacy and safety, therefore becomes a basic objective when it comes to the quality of care and the commitment of the facilities caring for patients. In this sense, therefore, research is increasingly focusing on finding treatment modalities that also carefully observe this parameter. In this logic there is a new development today, which adds to what is already available in this pathway. The Italian Medicines Agency (Aifa) has approved the new subcutaneous formulation of nivolumab in several solid tumours, in addition to and three further indications of the immuno-oncological drug in combination with ipilimumab in first-line metastatic colorectal cancer with mismatch repair deficiency or high microsatellite instability (dMMR/MSI-H), in combination with first-line chemotherapy in unresectable or metastatic urothelial carcinoma, and as monotherapy in the adjuvant treatment of muscle-invasive urothelial carcinoma.

"Immuno-oncology, over the last 15 years, has represented a 'tsunami' in cancer treatment, because it has changed the natural history of many tumours," explains Paolo Ascierto, director of the Complex Structure of Experimental Clinical Oncology of Melanoma - Immunotherapy and Innovative Therapies at the IRCCS Fondazione Pascale National Cancer Institute in Naples. Today innovation allows us to reach a further milestone, which is the subcutaneous administration of nivolumab, a simpler and faster formulation than intravenous infusion. It takes only a few minutes, compared to 30 minutes to an hour for the infusion, and no cannulae or venous catheters are needed. In this way, the treatment pathway is simplified, patients spend less time in hospital and the administration is easier'. Along the same lines are the patients' comments, voiced by Francesco De Lorenzo, president of Favo (Italian Federation of Voluntary Associations in Oncology). "Simplifying the way immunotherapy is administered has an immediate impact on patients and caregivers," he emphasises. "The main advantages include the lower psychological impact of treatment, because the subcutaneous injection is less invasive, and the reduction in hospital waiting times with benefits for quality of life. In addition, treatment is made easier for patients with difficult-to-access veins. There are also benefits for the National Health Service, because the workload of the staff is lightened, who can spend more time listening to and talking to patients, with an optimisation of resources in oncology day hospitals'.

Immuno-oncology has also changed clinical practice in colorectal cancer, more than 41,000 new cases in Italy in 2025. In particular, about 4% of patients with metastatic colorectal cancer have the mismatch repair defect or high instability of microsatellites, the protein complex responsible for correcting DNA replication errors. This defect, which in the past was recognised as a biological feature with a poor prognosis, becomes a positive predictive factor making it possible to select the subgroup of patients who respond to immunotherapy: today a combination of immunotherapy with nivolumab has been registered for these patients in the first line. "This is the first approved first-line immunotherapy combination in these patients," explains Sara Lonardi, Director of Oncology 1 at the Istituto Oncologico Veneto IRCCS in Padua, Italy. "In the CheckMate 8HW study, the first-line dual immunotherapy showed superior efficacy compared to monotherapy. Nivolumab plus only 4 administrations of low-dose ipilimumab reduced the risk of progression by 31% compared to nivolumab monotherapy, with an extremely good toxicity profile. The clinical benefit is significant: the 4-year follow-up indicates that 4 out of 5 patients are progression-free. Moreover, even for these patients, there is the option of subcutaneous administration of nivolumab - after the combination phase with ipilimumab - thus providing important advantages in terms of convenience and therapy management'.

Finally, immunotherapy is substantially changing the treatment scenario for bladder cancer, with an estimated 29,100 new diagnoses in 2025 in our country. AIFA has approved nivolumab as monotherapy for adjuvant treatment, i.e. after surgery, in patients with muscle-invasive urothelial carcinoma with tumour expression of PD L1 ≥ 1%, at high risk of recurrence after radical resection and ineligible for post-operative adjuvant chemotherapy with cisplatin. "For years, about half of patients with muscle-invasive urothelial carcinoma, despite early diagnosis allowing surgical removal of the tumour, have experienced disease recurrence, with few effective therapeutic options able to prevent it," says Fabio Calabrò, Director of Medical Oncology 1 at the IRCCS Regina Elena National Cancer Institute in Rome. In the CheckMate-274 study, nivolumab demonstrated a median disease-free survival of over 4.5 years, with a 42% reduction in the risk of recurrence or death compared to placebo. Aifa's approval changes clinical practice because it introduces a new standard of care post-surgery and, for these patients, it also adds the opportunity to access subcutaneous administration of immunotherapy'. Finally, Aifa approved nivolumab in combination with chemotherapy (cisplatin and gemcitabine) for the first-line treatment of adult patients with unresectable or metastatic urothelial carcinoma. According to Calabrò, 'in the CheckMate-901 trial, nivolumab in combination with cisplatin-based chemotherapy reduced the risk of death by 22%, demonstrating a median overall survival of 21.7 months compared to 18.9 months with chemotherapy alone. The particularly interesting finding also relates to the percentage of complete responses to therapy, i.e. the complete disappearance of the disease visible on radiological investigations. Some 22% of patients treated with the combination in fact reported a complete response that lasted a median of more than three years. It is the first chemo-immunotherapy combination to show such an improvement over the standard of care based on cisplatin-based combinations'.