(UroToday.com) The combination of cisplatin-based chemotherapy with immune checkpoint inhibitors has previously been extensively investigated in urothelial carcinoma. Using this combination in the neoadjuvant setting for patients with muscle-invasive urothelial carcinoma might improve pathological response but carries the risk of increased perioperative morbidity. At the 2021 American Society of Clinical Oncology Genitourinary Cancers Symposium (ASCO GU), Dr. Richard Cathomas presented preliminary results of SAKK 06/17 assessing safety and efficacy using perioperative cisplatin/gemcitabine plus durvalumab for patients with muscle-invasive urothelial carcinoma.
SAKK 06/17 is an open-label, single arm, phase II trial for patients with operable muscle-invasive urothelial carcinoma cT2-T4a/cN0-1. Treatment consists of four cycles of neoadjuvant cisplatin/gemcitabine Q3W in combination with four cycles of durvalumab 1500mg Q3W followed by resection. Durvalumab is continued after surgery Q4W for 10 cycles. The trial schema for SAKK 06/17 is as follows:
The primary endpoint for this trial is event free survival at 2 years. It was estimated that 58 patients are needed based on type I error of 10% and a power of 80% for H1 event-free survival at 2 years ≥ 65% compared to H0 event-free survival at 2 years ≤ 50%. For this analysis, Dr. Cathomas reported the secondary endpoints pathologic response rate, pathological complete response (ypT0 N0), and safety on the full analysis set.
There were 61 patients included between July 2018 and September 2019 at 12 sites (11 in Switzerland and 1 in Germany). The analysis cohort consists of 58 patients with a median age of 67.5 years (range: 33-81), 79% of whom were male, with the majority of patients having bladder urothelial carcinoma (95%; 5% upper tract/urethral urothelial carcinoma). There were 69% of patients that were cT2, 21% were cT3, and 10% were cT4 stage at diagnosis; 17% were cN1. 95% of patients received all four doses of neoadjuvant durvalumab, 81% received all four cycles of cisplatin/gemcitabine, and 17% switched to carboplatin. Resection was performed in 53 patients (91%; 51 radical cystectomy, 2 nephroureterectomy), four patients refused surgery, and one patient was unresectable. A negative margin (R0 resection) was achieved in 52 patients (98%). Postoperative complications included Clavien-Dindo III in 13 patients (24%) and IV in 5 patients (9%). The pathologic response rate was 60% (95% CI 46.0%-73.5%) with 18 patients achieving a pathologic complete response (34%; 95% CI 21.5%-48.3%) and 14 patients (26%) ypT1/ypTis:
In total, grade 3 and 4 adverse events during neoadjuvant treatment occurred in 48% and 27%, respectively. Adverse events related to durvalumab were grade 3 in 7 patients (12%) and grade 4 in one patient (2%).
Dr. Cathomas concluded this presentation of preliminary results of the SAKK 06/17 trial with the following take home messages:
- The pathologic complete response rate of 34% and pathologic response rate of 60% for neoadjuvant durvalumab plus cisplatin/gemcitabine confirm results from similar phase II trials (BLASST-1, HOG)
- Neoadjuvant durvalumab plus cisplatin/gemcitabine is feasible and can be completed in the vast majority of patients
- The triple combination is safe without unexpected toxicities
- High-grade post-operative complications (Clavien-Dindo >= IIIa 34%) are comparable to results from the PURE-01 study
- The final analysis for the primary endpoint (event free survival at 2 years) is expected in the first quarter of 2022
Presented by: Richard Cathomas, PD Dr. med, Department of Oncology, Cantonal Hospital Graubünden, Chur, Switzerland
Co-Authors: Sacha Rothschild, Stefanie Hayoz, Martin Spahn, Julian Schardt, Roland Seiler, Andreas Erdmann, Stefanie Aeppli, Nicolas Mach, Raeto Strebel, Boris A. Hadaschik, Dominik R. Berthold, Miklos Pless, Deborah Zihler, Mathias Schmid, Martina Schneider, Zuzanna Maniecka, Ulf Petrausch; Department of Oncology, Cantonal Hospital Graubünden, Chur, Switzerland; Department of Medical Oncology, University Hospital Basel, Basel, Switzerland; Swiss Group for Clinical Cancer Research, Bern, Switzerland; Hirslanden Klinik, Zürich, Switzerland; University Hospital Bern, Deparment of Oncology, Bern, Switzerland; University Hospital Bern, Bern, Switzerland; Kantonsspital Baden, Baden, Switzerland; Department of Oncology/Haematology, Cantonal Hospital St. Gallen, St.Gallen, Switzerland; Department of Oncology, University Hospital Geneva, Geneva, Switzerland; Kantonsspital Graubünden, Chur, Switzerland; Vancouver Prostate Centre, Vancouver, BC, Canada; Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland; Department of Oncology, Cantonal Hospital Winterthur, Winterthur, Switzerland; Department of Oncology and Hematology, Kantonsspital Aarau, Aarau, Switzerland; Stadtspital Triemli, Zurich, Switzerland; SAKK-Swiss Group for Clinical Cancer Research, Coordinating Center, Bern, Switzerland; SAKK Coordinating Center, Bern, Switzerland; OnkoZentrum Zurich, Zurich, Switzerland
Written by: Zachary Klaassen, MD, MSc – Urologic Oncologist, Assistant Professor of Urology, Georgia Cancer Center, Augusta University/Medical College of Georgia, Twitter: @zklaassen_md during the 2021 American Society of Clinical Oncology Genitourinary Cancers Symposium (#GU21), February 11th-February 13th, 2021