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.
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
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.The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.