Improving survival and reducing the risk of recurrence (and death) in muscle-invasive bladder cancer. These goals are possible thanks to the first pre-operative immunotherapy regimen with durvalumab. This is what emerges from the phase 3 NIAGARA study presented today during the presidential symposium of the European Society for Medical Oncology (Esmo) Congress 2024 which brings together thousands of oncologists from all over the world in Barcelona these days, and simultaneously published in The New England Journal of Medicine.
At a predefined interim analysis of the study, patients treated with the preoperative durvalumab regimen showed a 32% reduction in the risk of disease progression, recurrence, failure to complete scheduled surgery, or death compared to the comparator arm. The estimated median EFS was not reached in the durvalumab arm compared to 46.1 months in the comparator arm. An estimated 67.8% of patients treated with the durvalumab regimen were event-free at two years, compared to 59.8% in the comparator arm. Results from the secondary survival endpoint showed that the preoperative durvalumab regimen reduced the risk of death by 25% compared to neoadjuvant chemotherapy before radical cystectomy. The median survival was not reached in either arm. 82.2% of patients treated with the durvalumab regimen were alive at two years compared to 75.2% in the comparator arm.
“The NIAGARA study demonstrates that the addition of immunotherapy with durvalumab, before and after surgery, may represent an innovative strategy, capable of changing clinical practice for patients with operable infiltrating urothelial bladder cancer,” says Lorenzo Antonuzzo, Director of the Complex Structure of Clinical Oncology at the Careggi University Hospital, Department of Experimental and Clinical Medicine, University of Florence. “This immunotherapy regimen allows for significant improvements in the two main endpoints of the study, namely event-free survival and overall survival. The data on overall survival is particularly relevant in a complex patient population to treat, such as that affected by infiltrating urothelial bladder cancer. Although it is a neoplasm localized to the bladder, it is more aggressive than non-infiltrating cancer and can extend locally to invade the muscle layers and the entire bladder wall.”
In the study involving approximately 1000 patients, “neoadjuvant treatment, i.e. perioperative, consisting of chemoimmunotherapy and durvalumab monotherapy after surgery was used,” Antonuzzo continues. “The comparison arm is neoadjuvant chemotherapy. NIAGARA is the first registration study in which an immunotherapy regimen, before and after surgery, prolongs survival in this pathology.”
“The standard treatment, for about 20 years, has been neoadjuvant chemotherapy followed by surgery, but half of the patients experience disease recurrence or progression, so there is still an unmet clinical need – underlines Massimo Di Maio, president-elect of Aiom (Italian Association of Medical Oncology) -. Furthermore, in Italy, the treatment of operable infiltrating forms is varied, because there are patients who are treated directly with surgery. The important results of the NIAGARA study can constitute a stimulus to the use of neoadjuvant therapy in all patients. It should also be emphasized that the chemoimmunotherapeutic regimen is well tolerated and safe”.
In managing the disease “and to ensure the best therapeutic path, the multidisciplinary team is essential, which must include, among others, the radiologist, the surgeon, the oncologist, the urologist and the pathologist – concludes Di Maio -. Bladder cancer is one of the most frequent, in 2023 in Italy 29,700 new cases were estimated. It is a sneaky neoplasm, because in the initial stages it can be completely asymptomatic. The first warning signs are urinary symptoms, for example difficulty urinating and frequent urination, and the presence of hematuria, that is, blood in the urine. The main risk factor is cigarette smoking, to which is added professional exposure to certain carcinogenic substances, such as aromatic amines and nitrosamines”.
Bladder cancer is the ninth most common cancer worldwide, with more than 614,000 diagnoses each year. Muscle-invasive bladder cancer accounts for approximately one-quarter of bladder cancer cases. In the MIBC setting, approximately 117,000 patients are treated with standard of care. Standard therapy includes neoadjuvant chemotherapy and radical cystectomy. However, even after cystectomy, patients are subject to high recurrence rates and a poor prognosis. Approximately 50% of patients who undergo bladder removal surgery experience recurrence. Treatment options that prevent recurrence after surgery are greatly needed.
#Bladder #Cancer #PreOperative #Immunotherapy #Improves #Survival
