More than half of resected patients with muscle-invasive urothelial carcinoma achieve a pathologic response with durvalumab plus neoadjuvant cisplatin/gemcitabine in the phase 2 SAKK 06/17 trial.
Combining durvalumab (Imfinzi) with neoadjuvant gemcitabine/cisplatin followed by surgery and adjuvant durvalumab produced promising event-free survival (EFS) and overall survival (OS) among patients with muscle-invasive urothelial carcinoma, according to published findings from the phase 2 SAKK 06/17 trial (NCT03406650).
The study regimen produced a 2-year EFS rate of 75.7% (95% CI, 61.8%-85.1%) and a 3-year EFS rate of 73.4% (95% CI, 59.2%-83.4%); the median EFS was not reached. The OS rate at 2 years and 3 years, respectively, was 85.0% (95% CI, 72.3%-92.2%) and 80.8% (95% CI, 67.2%-89.2%). Among 51 patients with a R0 resection at surgery, the recurrence-free survival (RFS) rate was 83.4% (95% CI, 69.5%-91.3%) at 2 years and 80.9% (95% CI, 66.5%-89.6%) at 3 years following surgery.
Among 52 patients who underwent resection, the pathologic response rate (PaR) was 59.6% (95% CI, 45.1%-73.0%), and the pathologic complete response (pCR) rate was 32.7% (95% CI, 20.3%-47.1%). Additionally, the 2-year EFS rate among patients with stage ypT2 disease or lower was 97.0% (95% CI, 80.4%-99.5%).
“With regards to potential biomarkers of response to bladder cancer treatment, we could not find a significant correlation to PD-L1, MTAP, or SLFN11 status. Further translational research is ongoing and will be published in a separate manuscript,” the study authors wrote. “The outcome of several ongoing phase 3 trials will inform us if [neoadjuvant chemotherapy plus durvalumab followed by surgery and adjuvant durvalumab] can become standard of care for patients with localized [muscle-invasive urothelial carcinoma].”
In the open-label, single-arm SAKK 06/17 study, patients received 1000 mg/m2 of gemcitabine intravenously on days 1 and 8 plus 70 mg/m2 of cisplatin intravenously on day 1 of 4 cycles that repeated once every 3 weeks. Patients also received 1500 mg of intravenous neoadjuvant durvalumab starting on day 22 of chemotherapy for 4 doses once every 3 weeks. Additionally, adjuvant durvalumab was administered 4 to 12 weeks following surgery once every 4 weeks for up to 10 cycles.
The trial’s primary end point was the 2-year EFS rate. Secondary end points included EFS, OS, RFS following R0 resection, PaR, treatment feasibility, and adverse effects (AEs).
Patients with histologically confirmed urothelial carcinoma of the bladder, urethra, or upper urinary tract with no evidence of distant metastases were able to enroll on the trial. Those with upper tract disease were eligible for enrollment if they had positive urine cytology and tumor mass documented via urography.
The full analysis set consisted of 57 patients, and 52 were resected. Most patients in the full set analysis set were male (79%), had a World Health Organization performance status of 0 (86%), a primary tumor located in the bladder (95%), and stage cT2 disease at presentation (70%). Additionally, most patients had stage cN0 disease (84%) and pure urothelial carcinoma not otherwise specified (75%).
Overall, 98% of the study population completed 4 cycles of neoadjuvant gemcitabine/cisplatin, and 93% received the 4 planned cycles of neoadjuvant durvalumab. Additionally, 90% of patients completed surgery. Among those included in the full analysis set, 83% started adjuvant durvalumab in a timely manner, 64% of whom completed all 10 planned cycles.
Investigators reported treatment-related AEs in all patients that were possibly, probably, or definitely related to the study regimen. Grade 1, 2, 3, and 4 AEs related to durvalumab, respectively, occurred in 14%, 35%, 19%, and 7% of patients.
Common any-grade TRAEs during neoadjuvant treatment included fatigue (63%), nausea (53%), thrombocytopenia (49%), neutropenia (47%), and anemia (40%). Among 47 patients, immune-related AEs associated with adjuvant durvalumab of any grade included diarrhea (13%), dry skin (11%), and lipase or amylase increases (11%).
Cathomas R, Rothschild SI, Hayoz S, et al. Perioperative chemoimmunotherapy with durvalumab for muscle-invasive urothelial carcinoma: primary analysis of the single-arm phase II trial SAKK 06/17. J Clin Oncol. Published online August 17, 2023. doi:10.1200/JCO.23.00363