Impact of Neoadjuvant Durvalumab on Disease Recurrence and Survival in Muscle-Invasive Bladder Cancer
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Reviewed & translated by Dat Tien Nguyen, B.A, ScM.
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Posted on December 20th, 2024
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Current guidelines for bladder cancer recommend adjuvant cisplatin chemotherapy prior to radical cystectomy and pelvic lymph node dissection. However, 50% of patients experience relapse within three years. Durvalumab, a PD-1 inhibitor, can improve tumor clearance by blocking the immunosuppressive effects of cancer cells. A study funded by AstraZeneca was conducted to evaluate the effectiveness of adding durvalumab to the treatment regimen for managing muscle-invasive bladder cancer.
The phase 3 clinical trial included 1,063 patients diagnosed with muscle-invasive bladder cancer, based on the criteria outlined in the AJCC Cancer Staging Manual. Only participants with a minimum creatinine clearance rate of 40 mL per minute per 1.73 m² of body surface area were eligible for enrollment. Patients were randomly assigned to receive either four cycles of placebo or neoadjuvant durvalumab at a dose of 1,500 mg every three weeks. All participants, regardless of group, also received standard gemcitabine–cisplatin neoadjuvant chemotherapy, administered at 1,000 mg and 70 mg per m² of body surface area every three weeks. After completing the neoadjuvant treatments, patients underwent radical cystectomy surgery. Observation at 24 weeks post-surgery showed that patients treated with durvalumab in addition to the standard cisplatin regimen had a 32% reduction in the risk of disease recurrence and a survival rate of 74.5%, significantly higher than the 68.1% survival rate in those treated with cisplatin alone. The authors noted that recent findings from other studies have shown nivolumab and the combination of enfortumab vedotin with pembrolizumab to be effective adjuvants in managing bladder cancer. Therefore, future studies may compare the effectiveness of these treatments with durvalumab as a neoadjuvant therapy.
The phase 3 clinical trial included 1,063 patients diagnosed with muscle-invasive bladder cancer, based on the criteria outlined in the AJCC Cancer Staging Manual. Only participants with a minimum creatinine clearance rate of 40 mL per minute per 1.73 m² of body surface area were eligible for enrollment. Patients were randomly assigned to receive either four cycles of placebo or neoadjuvant durvalumab at a dose of 1,500 mg every three weeks. All participants, regardless of group, also received standard gemcitabine–cisplatin neoadjuvant chemotherapy, administered at 1,000 mg and 70 mg per m² of body surface area every three weeks. After completing the neoadjuvant treatments, patients underwent radical cystectomy surgery. Observation at 24 weeks post-surgery showed that patients treated with durvalumab in addition to the standard cisplatin regimen had a 32% reduction in the risk of disease recurrence and a survival rate of 74.5%, significantly higher than the 68.1% survival rate in those treated with cisplatin alone. The authors noted that recent findings from other studies have shown nivolumab and the combination of enfortumab vedotin with pembrolizumab to be effective adjuvants in managing bladder cancer. Therefore, future studies may compare the effectiveness of these treatments with durvalumab as a neoadjuvant therapy.