On March 28, 2025, the Food and Drug Administration approved durvalumab (Imfinzi, AstraZeneca) to be used with gemcitabine and cisplatin as a first treatment, followed by durvalumab alone as a follow-up treatment after surgery, for patients with muscle-invasive bladder cancer (MIBC).
Effectiveness and Safety
The effectiveness was evaluated in NIAGARA (NCT03732677), a Phase III trial where 1,063 patients who could have radical cystectomy and had not received any previous treatment for bladder cancer were randomly assigned to either get neoadjuvant durvalumab with chemotherapy, followed by adjuvant durvalumab after surgery, or just neoadjuvant chemotherapy followed by surgery.
Patients were randomly assigned (1:1) to either get neoadjuvant durvalumab along with chemotherapy, followed by adjuvant durvalumab after surgery, or to receive only neoadjuvant chemotherapy followed by surgery.
The primary efficacy endpoint was event-free survival (EFS) assessed by blinded independent central review. Overall survival (OS) constituted a supplementary effectiveness outcome. During a predetermined interim analysis, the trial exhibited a statistically significant enhancement in event-free survival (EFS) and overall survival (OS).
The average time without events (EFS) was not reached in the durvalumab plus chemotherapy group, but it was 46.1 months in the chemotherapy group, with a hazard ratio of 0.68 and a very low p-value. The average overall survival was also not reached in either group, with a hazard ratio of 0.75 and a p-value of 0.0106. The median overall survival was not attained in either group (hazard ratio 0.75 [95% CI: 0.59, 0.93]; two-sided p-value=0.0106).
Adverse effects aligned with previous experiences involving durvalumab and platinum-based chemotherapy.
The advised dosage of durvalumab for patients weighing ≥30 kg is 1,500 mg every 3 weeks in conjunction with chemotherapy (neoadjuvant treatment) and 1,500 mg as a monotherapy every 4 weeks (adjuvant treatment). The advised dosage of durvalumab for patients weighing less than 30 kg is 20 mg/kg in conjunction with chemotherapy every three weeks (neoadjuvant treatment) and 20 mg/kg as a monotherapy every four weeks (adjuvant treatment). Treatment should persist until disease development that prevents definitive surgery, recurrence, severe toxicity, or a maximum of 8 cycles post-surgery.
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Dr. Nishant Mittal is a highly accomplished researcher with over 13 years of experience in the fields of cardiovascular biology and cancer research. His career is marked by significant contributions to stem cell biology, developmental biology, and innovative research techniques.
Research Highlights
Dr. Mittal's research has focused on several key areas:
1) Cardiovascular Development and Regeneration: He studied coronary vessel development and regeneration using zebrafish models1.
2) Cancer Biology: At Dartmouth College, he developed zebrafish models for studying tumor heterogeneity and clonal evolution in pancreatic cancer.
3) Developmental Biology: His doctoral work at Keio University involved identifying and characterizing medaka fish mutants with cardiovascular defects.
4) Stem Cell Research: He investigated the effects of folic acid on mouse embryonic stem cells and worked on cryopreservation techniques for hematopoietic stem cells.
Publications and Presentations
Dr. Mittal has authored several peer-reviewed publications in reputable journals such as Scientific Reports, Cardiovascular Research, and Disease Models & Mechanisms1. He has also presented his research at numerous international conferences, including the Stanford-Weill Cornell Cardiovascular Research Symposium and the Weinstein Cardiovascular Development Conference.
In summary, Dr. Nishant Mittal is a dedicated and accomplished researcher with a strong track record in cardiovascular and cancer biology, demonstrating expertise in various model systems and a commitment to advancing scientific knowledge through innovative research approaches.
