The integration of immunotherapy in the perioperative setting of muscle-invasive urothelial carcinoma (MIUC) appears promising. SAKK 06/17 investigated the addition of neoadjuvant durvalumab to gemcitabine/cisplatin (GC) chemotherapy followed by radical surgery and adjuvant checkpoint inhibition with durvalumab.
SAKK 06/17 was an investigator-initiated, open-label, single-arm phase II study including cisplatin-fit patients with stage cT2-T4a cN0-1 operable MIUC. Four cycles of neoadjuvant GC in combination with four cycles of durvalumab (start with GC cycle 2) were administered, followed by radical surgery. Adjuvant durvalumab was given for 10 cycles. The primary end point was event-free survival (EFS) at 2 years.
Sixty one patients were accrued at 12 sites. The full analysis set consisted of 57 patients, 54 (95%) had bladder cancer. Median follow-up was 40 months. The primary end point was met, with EFS at 2 years of 76% (one-sided 90% CI [lower bound], 67%; two-sided 95% CI, 62 to 85). EFS at 3 years was 73% (95% CI, 59 to 83). Complete pathologic response in resected patients (N = 52) was achieved in 17 patients (33%), and 31 (60%) had pathologic response <ypT2 ypN0. Overall survival (OS) was 85% (95% CI, 72 to 92) at 2 years and 81% (95% CI, 67 to 89) at 3 years. Grade 3 and 4 treatment-related adverse events (TRAEs) during neoadjuvant treatment occurred in 42% and 25%, respectively. TRAEs related to adjuvant durvalumab were grade 3 in 5 (11%) and grade 4 in 2 (4%) patients.
The addition of perioperative durvalumab to the standard of care for patients with resectable MIUC results in a high EFS and OS at 2 years.
Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2023 Aug 17 [Epub ahead of print]
Richard Cathomas, Sacha I Rothschild, Stefanie Hayoz, Lukas Bubendorf, Berna C Özdemir, Bernhard Kiss, Andreas Erdmann, Stefanie Aeppli, Nicolas Mach, Räto T Strebel, Boris Hadaschik, Dominik Berthold, Hubert John, Deborah Zihler, Mathias Schmid, Ilaria Alborelli, Martina Schneider, Jana Musilova, Martin Spahn, Ulf Petrausch
Division of Oncology/Hematology, Kantonsspital Graubünden, Chur, Switzerland., Department of Medical Oncology and Comprehensive Cancer Center, University Hospital Basel, Basel, Switzerland., Competence Center of SAKK, Bern, Switzerland., Institute of Medical Genetics and Pathology, University Hospital Basel, Basel, Switzerland., Department of Oncology, Bern University Hospital, Bern, Switzerland., Department of Urology, Bern University Hospital, Bern, Switzerland., Department of Oncology/Hematology, Kantonsspital Baden, Baden, Switzerland., Department of Oncology, University Hospital HUG, Geneva, Switzerland., Department of Oncology, Kantonsspital St Gallen, St Gallen, Switzerland., Division of Urology, Kantonsspital Graubünden, Chur, Switzerland., Department of Urology, University Hospital Essen, Essen, Germany., Department of Oncology, University Hospital CHUV, Lausanne, Switzerland., Department of Urology, Kantonsspital Winterthur, Winterthur, Switzerland., Department of Oncology, Kantonsspital Aarau, Aarau, Switzerland., Department of Oncology, Triemlispital, Zürich, Switzerland., Onkozentrum Zürich, Zürich, Switzerland.