Extending OS with perioperative durvalumab in a cisplatin-eligible elderly patient with MIBC

Presentation and investigation
A 74-year-old nonsmoker and non­drinker presented to a private urologist in January 2025 with gross haematu­ria. Aside from benign prostatic hyper­plasia, he was well and physically fit. On 14 January 2025, a CT scan re­vealed a large mass measuring 5.8 cm with full-thickness infiltration into the bladder wall, consistent with clinical T3 disease. A metastatic lymph node (LN) of approximately 1.0 cm was not­ed in the left internal iliac region, with no distant metastases.

One week later, the patient re­ceived transurethral resection of the bladder tumour (TURBT). Pathology results confirmed locally advanced, high-grade, muscle-invasive, stage III (cT3N1M0) urothelial carcino­ma. Neither PD-L1 expression nor circulating-tumour DNA (ctDNA) level were assessed at the time. Eastern Cooperative Oncology Group (ECOG) performance status was 0. Renal func­tion was normal.

Treatment and response
On 7 February 2025, the patient was referred to our clinic for further treatment. The patient was prescribed the NIAGARA regimen (neoadjuvant intravenous [IV] durvalumab 1,500 mg plus gemcitabine–cisplatin Q3W for four cycles, followed by radical cystectomy; adjuvant durvalumab was planned, but the patient was lost to follow-up and did not receive it), in view of its reported overall survival (OS) and event-free sur­vival (EFS) benefits.¹

Overall, the patient tolerated the NI­AGARA regimen well, with only mild or moderate adverse events (AEs) report­ed. During the first two cycles of neoad­juvant treatment, the patient developed a grade 1–2 rash that resolved with oral antihistamines, with no resultant delay in chemoimmunotherapy. An IV anti­histamine was given as premedication from cycle 3 onwards, which effectively prevented any subsequent rash. In cy­cle 4, the patient experienced grade 1 anaemia, with haemoglobin level drop­ping from 13.5 to 10.6 g/dL, which was likely attributable to poor appetite and chemotherapy-related bone marrow suppression. Body weight, platelet count, white blood cell counts, and renal function remained normal throughout four cycles of neoadjuvant treatment.

On 22 April 2025, a week after the final cycle of neoadjuvant treatment, a PET-CT scan showed shrinkage of the bladder mass from 5.8 to 2 cm, reso­lution of the left internal iliac LN, and no distant metastases. The patient subse­quently underwent radical cystectomy with pelvic lymphadenectomy dissec­tion at a public hospital and achieved pathologic complete response (pCR). Despite a short episode of paralytic ileus after surgery, the patient recovered well and was discharged.

After surgery, the patient was man­aged by a urologist at the public hospi­tal. As of June 2025, he remained well and fully ambulatory with no evidence of disease progression.

Discussion
The clinical decision to initiate perioperative durvalumab and neoad­juvant chemotherapy in our physically fit patient was based on survival ben­efits observed in the phase III, global, open-label, randomized NIAGARA trial in cisplatin-eligible patients with muscle-invasive bladder cancer (MIBC).¹

In NIAGARA, patients were ran­domized 1:1 to receive periopera­tive durvalumab plus gemcitabine– cisplatin Q3W for four cycles, followed by radical cystectomy and adjuvant durvalumab Q4W for eight cycles (n=533; durvalumab group), or to receive neoadjuvant gemcitabine– cisplatin alone followed by radical cys­tetomy (n=530; comparison group).

At 24 months, the durvalumab group had significantly higher es­timated rates of EFS (67.8 vs 59.8 percent; hazard ratio [HR], 0.68; 95 percent confidence interval [CI], 0.56– 0.82; p<0.001) and OS (82.2 vs 75.2 percent; HR, 0.75; 95 percent CI, 0.59–0.93; p=0.01) vs the compari­son group. (Figure) Both the EFS and OS benefits were consistent across prespecified subgroups, including pa­tients with high or low/no PD-L1 ex­pression at baseline.¹

The intention-to-treat analysis showed a 10 percent increase in pCR rate – a strong prognostic indicator for improved EFS and OS outcomes – in the durvalumab vs comparison group (37.3 vs 27.5 percent; risk ratio, 1.34; 95 percent CI, 1.13–1.60).^1,2

Although ctDNA status was not evaluated in our patient, it was anoth­er strong prognostic factor at baseline and both before and after cystectomy in NIAGARA.³ Routine evaluation of ctDNA status is suggested if cost is not a concern.

In my practice, I generally prefer perioperative immunotherapy plus neoadjuvant chemotherapy over adjuvant-only immunotherapy. The combination of chemotherapy and im­munotherapy represents a promising, synergistic approach to improve treat­ment outcomes. Chemotherapy can directly kill tumour cells and promote the release of tumour antigens, which may help convert “cold” (immune-desert) tumours to “hot” (immune-inflamed) tumours. By altering the tumour microenvironment, chemo­immunotherapy boosts lymphocyte-mediated immune responses against tumour antigens.^4,5 The synergistic effect of perioperative durvalumab and neoadjuvant chemotherapy may explain the pCR and OS gains in the NIAGARA trial.

Overall, the safety profile of the NI­AGARA regimen was consistent with individual safety profiles of durvalumab and gemcitabine–cisplatin. The pro­portion of patients with AEs leading to treatment discontinuation during the neoadjuvant period was approximate­ly the same in both treatment groups (durvalumab vs comparison, 14.9 vs 15.2 percent), and AEs leading to dis­continuation of adjuvant durvalumab therapy were infrequent (7.8 percent).¹

Our patient experienced grade 1–2 rash – an immune-mediated AE that occurred in 2.3 percent of durvalumab-treated patients in NI­AGARA.¹ Oral antihistamines were prescribed based on recommenda­tions of international guidelines.^6,7 As demonstrated in our case, IV antihis­tamines administered as premedica­tion before each cycle can effectively prevent rash.

In general, I prefer using periop­erative immunotherapy for cisplatin-eligible patients with MIBC. However, it is important to balance risks and ben­efits. For example, the NIAGARA reg­imen requires a creatinine clearance ≥40 mL/min/1.73 m² and patients to be medically fit.¹ Multidisciplinary team discussions are therefore essen­tial to identify suitable perioperative regimens for patients and to manage treatment-related AEs.