Perioperative chemoimmunotherapy with durvalumab (Durva) in combination with cisplatin/gemcitabine (Cis/Gem) for operable muscle-invasive urothelial carcinoma (MIUC): Preplanned interim analysis of a single-arm phase II trial (SAKK 06/17).

Authors

null

Richard Cathomas

Department of Oncology, Cantonal Hospital Graubünden, Chur, Switzerland

Richard Cathomas , Ulf Petrausch , Stefanie Hayoz , Martina Schneider , Julian Andreas Schardt , Roland Seiler , Andreas Erdmann , Sacha Rothschild , Stefanie Aeppli , Nicolas Mach , Raeto Strebel , Boris A. Hadaschik , Dominik R. Berthold , Miklos Pless , Deborah Zihler , Mathias Schmid , Christine Biaggi Rudolf , Martin Spahn

Organizations

Department of Oncology, Cantonal Hospital Graubünden, Chur, Switzerland, OnkoZentrum Zurich, Zurich, Switzerland, Swiss Group for Clinical Cancer Research, Bern, Switzerland, SAKK-Swiss Group for Clinical Cancer Research, Coordinating Center, Bern, Switzerland, University Hosital Bern, Bern, Switzerland, University Hospital Bern, Bern, Switzerland, Kantonsspital Baden, Baden, Switzerland, Medical Oncology, Department of Internal Medicine, University Hospital Basel, Basel, Switzerland, Department of Oncology/Haematology, Cantonal Hospital St. Gallen, St.Gallen, Switzerland, Hôpitaux Universitaires de Genève, Geneva, Switzerland, Kantonsspital Graubünden, Chur, Switzerland, University of Duisburg-Essen, Essen, Germany and Ruprecht-Karls-University, Heidelberg, Germany, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland, Department of Oncology, Kantonsspital Winterthur, Winterthur, Switzerland, Department of Oncology and Hematology, Kantonsspital Aarau, Aarau, Switzerland, Stadtspital Triemli, Zurich, Switzerland, Hirslanden Klinik, Zurich, Switzerland

Research Funding

Pharmaceutical/Biotech Company
Astra Zeneca, SAKK Swiss Group for Clinical Cancer Research.

Background: Cisplatin-based neoadjuvant chemotherapy followed by surgery is the standard of care for patients (pts) with MIUC but relapse rates remain high. Immune checkpoint inhibitors have demonstrated efficacy in advanced urothelial carcinoma (UC). We hypothesize that the integration of the PD-L1 inhibitor durvalumab into perioperative management of MIUC improves outcome. Methods: SAKK 06/17 is an open label single arm phase II study including 61 pts. Operable MIUC cT2-T4a cN0-1 pts without contraindication for Cis were eligible. Four cycles of preoperative Cis/Gem q3w are administered in combination with 4 cycles Durva 1500mg q3w starting at cycle 2. Durva is continued after surgery q4w for 10 cycles. Primary endpoint is event free survival at 2 years. We report a preplanned interim analysis of the secondary endpoints safety, pathological complete remission ypT0 N0 (pCR,) and pathological response rate (PaR, defined as ≤ypT1N0) on the first 30 resected pts. Results: Among 34 eligible pts (27M, 7F; median age 70, range 41-81 years) included from 07/18 – 02/19, 33 pts (97%) had primary bladder cancer and 1 pt had upper tract UC. Clinical T2, T3, T4 and TxN1 stage were present at diagnosis in 68%, 18%, 15% and 15%, respectively. Four cycles of chemo-immunotherapy were completed per protocol in 34 pts (100%). No tumor progression was noted at preoperative restaging. AE related to Durvalumab were G3 in 5 pts (15%) and G4 in 3 pts (9%). Surgery was performed as planned in 30 pts (88%), 3 pts refused surgery and 1 pt had a frozen pelvis. Operation technique was open in 20 pts (67%) and laparoscopic/robot-assisted in 10 pts (33%). Postoperative complications included Clavien-Dindo III in 6 pts (20%) and IV in 2 pts (7%) with infections being most common (5 pts, 17%). pCR was found in 9 pts (30%) and additional 6 pts (20%) had ypT1/ypTis for a PaR of 50%. Conclusions: The combination of Cis/Gem and Durva as neoadjuvant treatment for MIUC is feasible with manageable toxicities and pCR and PaR rates in the expected range. The rate of postoperative complications warrants further close follow up. Clinical trial information: 2017-003565-10.

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Abstract Details

Meeting

2020 Genitourinary Cancers Symposium

Session Type

Poster Session

Session Title

Poster Session B: Prostate Cancer; Urothelial Carcinoma; Penile, Urethral, Testicular, and Adrenal Cancers

Track

Urothelial Carcinoma,Adrenal Cancer,Penile Cancer,Prostate Cancer - Advanced,Prostate Cancer - Localized,Testicular Cancer,Urethral Cancer

Sub Track

Therapeutics

Clinical Trial Registration Number

2017-003565-10

Citation

J Clin Oncol 38, 2020 (suppl 6; abstr 499)

Abstract #

499

Poster Bd #

H22

Abstract Disclosures