Bladder cancer: efficiency booster, immunotherapy, a concrete hope against invasive forms

Cancer de la vessie : l’immunothérapie, un espoir concret contre les formes invasives

In light of the results of the NIAGARA trial, the new immunotherapy durvalumab should quickly change the prognosis in certain bladder cancers. In France, 1,500 patients with aggressive bladder cancer, i.e. invading the bladder muscle, could benefit from it, with the hope of better overall survival and without tumor progression.

This study on patients with muscle-invasive bladder cancer (“infiltrating the muscle” in medical parlance). “Several molecules have been tested before, but all have failed, which explains the international community's interest in the monoclonal antibody durvalumab “, explains the specialist.

Boosting the effectiveness of chemotherapy

Bladder cancer affects around 13,000 to 14,000 new patients per year in France, with tobacco being one of the main risk factors. “What interests us here, he continues, These are the severe forms of the disease, particularly muscle-invasive bladder cancers, which affect around 4,000 patients per year. Of these, 3,000 are eligible for radical cystectomy. This is the standard treatment which involves removing the bladder in order to eliminate the tumour, in the hope of achieving complete remission. However, around 25% to 50% of patients have a recurrence after cystectomy combined with chemotherapy. To reduce this risk, only around 1,500 can receive effective chemotherapy, including cisplatin. Hence the interest in boosting the effectiveness of chemotherapy with an additional treatment, in this case durvalumab."

Improving the prognosis after chemotherapy and surgery

In the phase 3 NIAGARA trial, participants with muscle-invasive bladder cancer were divided into two groups, one receiving standard chemotherapy (gemcitabine + cisplatin), the other the same chemotherapy but with the addition of durvalumab, an immunotherapy.

How Immunotherapy Works ? Bladder cancer uses mechanisms such as interactions between ligands and receptors (such as PD-1 and PDL-1) to prevent the immune system's lymphocytes from attacking it. Immunotherapies work by removing this “protection” so that cancer cells are recognized and attacked by the immune system again.

In the case of durvalumab, it worked: immunotherapy generated a prolonged antitumor response through activation of the immune system.

A significant improvement in patient prognosis

Patients treated with the perioperative regimen including durvalumab had a 32% reduction in the risk of disease progression, recurrence, no surgery, or death compared with the comparator group: 67.8% of patients treated with the durvalumab regimen were event-free at two years, versus 59.8% in the comparator group.

For overall survival, the perioperative regimen with durvalumab reduced the risk of death by 25% compared with neoadjuvant chemotherapy with radical cystectomy: 82.2% of patients treated with the durvalumab regimen were alive at two years, versus 75.2% in the comparator group.

In summary, the data from The NIAGARA study showed improvements in event-free survival and overall survival, with more than 80% of patients treated perioperatively with durvalumab still alive after two years. “This is the first immunotherapy protocol in combination with surgery to significantly extend overall survival in muscle-invasive bladder cancer“, says Professor Neuzillet.

No additional toxicity

The good news is that no additional toxicity due to the addition of durvalumab was observed. Professor Neuzillet is convinced: “this is a real turning point, and it is therefore likely that treatment recommendations will evolve quickly to include the results of the NIAGARA study. Thus, any patient who is offered chemotherapy (based on gemcitabine and cisplatin) in a neoadjuvant setting could benefit from the addition of durvalumab to improve the prognosis. This trial further validates the strategy aimed at accelerating cancer treatment as early as possible in order to maximize the benefits for patients.”

In concrete terms, the NIAGARA study provides for four cycles of chemotherapy and preoperative immunotherapy (or even fewer in the event of signs of progression). After surgery (radical cystoscopy), eight cycles of immunotherapy are given to maintain the effect of durvalumab. The total treatment lasts less than a year.

* Imfinzi (durvalumab)/AstraZeneca