Iyer G, et al. - Authors evaluated the effectiveness and tolerability of 6 cycles of neoadjuvant dose-dense gemcitabine and cisplatin (ddGC) in patients with muscle-invasive bladder cancer (MIBC). For the treatment of patients with MIBC, 6 cycles of ddGC was an active, well-tolerated neoadjuvant regimen. Chemosensitivity, durable response and superior long-term survival were strongly predicted with the presence of a putative deleterious DDR gene alteration in pretreatment tumour tissue.

Methods

• In this prospective, multicenter phase II study, experts administered ddGC (gemcitabine 2,500 mg/m²on day 1 and cisplatin 35 mg/m²on days 1 and 2) to the patients every 2 weeks for 6 cycles followed by RC.
• They noted pathologic downstaging to non-muscle-invasive disease (< pT2N0) as the primary end point.
• They deemed the patients who did not undergo RC as nonresponders.
• To identify predictors of chemosensitivity, pretreatment tumors underwent next-generation sequencing.

Results

• As per data, 49 patients were enrolled from 3 institutions.
• Findings suggested that the primary end point was met, with 57% of 46 evaluable patients downstaged to < pT2N0.
• Researchers noted correlation of a pathologic response with improved recurrence-free survival and overall survival.
• Toxicity-related dose modifications were required in 19 (39%).
• All 6 planned cycles were completed by 67% of patients.
• Results demonstrated that failure to undergo RC as a result of chemotherapy-associated toxicities was not seen in any patients.
• Anemia was the most frequent treatment-related toxicity (12%; grade 3).
• They found an association of the presence of a presumed deleterious DNA damage response (DDR) gene alteration with chemosensitivity (positive predictive value for < pT2N0 [89%]).
• Recurrence was not seen in any patient with a deleterious DDR gene alteration at a median follow-up of 2 years.