- Neoadjuvant dose-dense gemcitabine and cisplatin (6 cycles) was well-tolerated and effective in patients with muscle-invasive bladder cancer (MIBC).
- The presence of deleterious DNA damage response (DDR) gene alterations strongly predicted chemosensitivity.
Why this matters
- These findings challenge the standard 3-4 cycles of neoadjuvant therapy (NAT).
- Detection of deleterious DDR gene alterations may help identify patients most likely to benefit from neoadjuvant chemotherapy.
- Multicenter phase 2 study of 49 patients with MIBC who received gemcitabine (2500 mg/m2 on day 1) and cisplatin (35 mg/m2 on days 1 and 2) every 2 weeks for 6 cycles, followed by radical cystectomy (RC).
- Funding: Zena and Michael A. Wiener Research and Therapeutic Program in Bladder Cancer.
- Median follow-up, 25.6 months.
- 57% of 46 evaluable patients downstaged to
- Pathological response rate was 62% in patients who underwent RC.
- Median recurrence-free survival (RFS) and OS were not reached.
- 39% of patients required toxicity-related dose modifications or discontinuation.
- 37% of patients experienced treatment-related grade 3-4 toxicities; anemia was the most common (12%).
- Positive predictive value of deleterious DDR gene alteration for response was 89%.
- 2-year RFS was higher in patients with deleterious DDR gene alterations vs those without (100% vs 61%; Plog-rank=.07).
- Single-group study.