In a Swiss phase II study (SAKK 06/17) reported in the Journal of Clinical Oncology, Richard Cathomas, MD, and colleagues found that the addition of perioperative durvalumab to neoadjuvant chemotherapy resulted in improved event-free and overall survival in patients with muscle-invasive urothelial carcinoma.
Study Details
In the investigator-initiated multicenter trial, 57 patients with stage cT2–T4a cN0–1 operable muscle-invasive urothelial carcinoma enrolled between July 2018 and September 2019 received four 3-week cycles of neoadjuvant gemcitabine (1,000 mg/m2 on day 1 and 8) and cisplatin (70 mg/m2 on day 1) plus four cycles of durvalumab at 1,500 mg every 3 weeks (starting at chemotherapy cycle 2). Patients underwent radical surgery and received 10 cycles of adjuvant durvalumab at 1,500 mg every 4 weeks.
The primary endpoint of the trial was event-free survival at 2 years. The null hypothesis was a lower bound of the 90% confidence interval of 50%.
Richard Cathomas, MD
Key Findings
Median follow-up was 40 months (95% confidence interval [CI] = 39–40 months). Event-free survival at 2 years was 76% (lower bound of 90% CI = 67%; 95% CI = 62%–85%). Event-free survival at 3 years was 73% (95% CI = 59%–83%).
Among 52 patients who underwent resection, pathologic complete response was observed in 17 (33%), and 31 (60%) had pathologic response ≤ ypT2 ypN0. Among these patients, 2-year event-free survival was 97.0% (95% CI = 80.4%–99.5%).
Among the 52 patients undergoing surgery, 51 had R0 resection; among them, recurrence-free survival was 83.4% (95% CI = 69.5%–91.3%) at 2 years and 80.9% (95% CI = 66.5%–89.6%) at 3 years. Overall survival was 85% (95% CI = 72%–92%) at 2 years and 81% (95% CI = 67%–89%) at 3 years.
During neoadjuvant treatment, grade 3 and 4 treatment-related adverse events occurred in 42% and 25% of patients, respectively. Adjuvant treatment-related adverse events were grade 3 in 11% of patients and grade 4 in 4%.
The investigators concluded, “The addition of perioperative durvalumab to the standard of care for patients with resectable muscle-invasive urothelial carcinoma results in a high event-free survival and overall survival at 2 years.”
Dr. Cathomas, of the Division of Oncology/Hematology, Cantonal Hospital Graubünden, Chur, Switzerland, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by AstraZeneca. For full disclosures of the study authors, visit ascopubs.org.
