TOPLINE:

In a phase 2 study, neoadjuvant sacituzumab govitecan plus pembrolizumab achieved a promising clinical complete response rate and had a favourable safety profile in patients with muscle-invasive bladder cancer (MIBC) who were ineligible for or refused cisplatin-based neoadjuvant chemotherapy, enabling bladder preservation in approximately 40% of patients.

METHODOLOGY:

• Researchers conducted a single-arm phase 2 study at IRCCS San Raffaele Hospital in Milan, Italy, and enrolled 49 patients (median age, 66 years) with newly diagnosed MIBC (stage cT2-cT3bN0M0) who were ineligible for or declined cisplatin-based neoadjuvant chemotherapy and were scheduled for radical cystectomy.
• Participants received four cycles of intravenous pembrolizumab 200 mg on day 1 and intravenous sacituzumab govitecan 7.5 mg/kg on days 1 and 8 for every 3 weeks. Planned surgery was radical cystectomy within 4-6 weeks; patients refusing radical cystectomy were offered a redo-transurethral resection of the bladder tumour (re‑TURBT) after multidisciplinary discussion and then 13 cycles of intravenous pembrolizumab 200 mg every 3 weeks after surgery.
• Tumour biomarkers were analysed with comprehensive genomic profiling and transcriptome-wide analyses using the Decipher Bladder genomic subtyping classifier to evaluate associations between molecular features and clinical complete response.
• The primary endpoint was the clinical complete response rate, defined as negative imaging and no viable residual disease at re-TURBT; secondary endpoints included overall pathologic response, event-free survival, bladder-intact event-free survival, and safety. The median follow-up duration was 14 months.
• Overall, four patients experienced a disease progression and started a second-line systemic therapy, 29 patients underwent re-TURBT, and 16 patients had a radical cystectomy.

TAKEAWAY:

• Overall, 19 patients (39%) achieved a clinical complete response after neoadjuvant therapy, although two among them developed intravesical relapse. None of the patients in the re-TURBT cohort developed distant metastases.
• Overall pathologic response (downstaging to ypT≤1N0-x) was achieved in 25 patients (51%). The 12-month event-free survival and 12-month metastasis-free survival in the intention-to-treat population were 71% and 74%, respectively. The 12-month bladder-intact event-free survival was 38% in the intention-to-treat population, 91% in patients with a clinical complete response, and 6% in the remaining patients.
• The clinical complete response rate was higher in patients with luminal subtype tumours vs non-luminal subtype tumours (57% vs 33%; P = .073). ERBB2 genomic alterations were more frequent in patients with vs without a clinical complete response (42% vs 14%; P = .55).
• Eight patients (16%) experienced treatment‑related adverse events of grade 3, the most common being diarrhoea in four patients. No treatment‑related adverse events of grades 4 and 5 were reported. Serious treatment‑related adverse events occurred in three patients (6%): two cases of bullous pemphigoid and one case of colitis.

IN PRACTICE:

"The primary analysis results from the SURE-02 trial show, for the first time, a benefit of using a perioperative antibody-drug conjugate plus immune-checkpoint inhibitor combination in a bladder-sparing approach for patients with muscle-invasive bladder cancer," the authors of the study wrote.

SOURCE:

This study was led by Andrea Necchi, MD, IRCCS San Raffaele Hospital, Comprehensive Cancer Center, Milan, Italy, and it was published online on February 27, 2026, in The Lancet Oncology.

LIMITATIONS:

This study had several limitations including its single-arm, single-centre design, the relatively small sample size, and the relatively short median follow-up duration, which limited the assessment of long-term outcomes and the full spectrum of delayed treatment-related adverse events, particularly those associated with adjuvant pembrolizumab. The high proportion of patients who refused cisplatin-based chemotherapy coupled with the absence of patients with Eastern Cooperative Oncology Group performance status 2 may have made comparisons with other trials difficult.

DISCLOSURES:

This study was funded by Merck Sharp & Dohme LLC, a subsidiary of Merck & Co, Inc, and Gilead Sciences. Necchi reported receiving institutional research funding or grants from AstraZeneca, Bristol Myers Squibb, Gilead, Ipsen, and Merck, as well as consulting or advisory fees from Astellas, AstraZeneca, Bristol Myers Squibb, CatalYm, Gilead, Johnson & Johnson, Samsung Bioepis, Bicycle Therapeutics, and Merck; serving in a leadership role for the Global Society of Rare Genitourinary Tumors; and being an associate editor for the Journal of Clinical Oncology. Full disclosures are noted in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.