Patients with bladder cancer (BC) who are cisplatin ineligible or have unresectable disease have limited treatment options. Previously, we showed targeting programmed death-ligand 1 (PD-L1) with durvalumab (durva) and radiation therapy (RT) combination was safe in BC.
We now report results from a phase II study evaluating the toxicity and efficacy of durva and RT in localized BC.
This is a single-arm, multi-institutional phase II study; N=26. Enrolled patients had pure or mixed urothelial BC (T2-4 N0-2 M0) with unresectable tumors and were unfit for surgery or cisplatin ineligible. Patients received durva concurrently with RT ×7 weeks, followed by adjuvant durva × 1 year.
(A) progression-free survival (PFS) at 1 year and (B) disease control rate (DCR) post adjuvant durva. Key secondary endpoints: (A) complete response (CR) post durvaRT (8 weeks), (B) overall survival (OS), (C) PFS and (D) toxicity. Correlative studies included evaluation of baseline tumor and blood (baseline, post durvaRT) for biomarkers.
Median follow-up was 27 months. Evaluable patients: 24/26 post durvaRT, 22/26 for DCR post adjuvant durva, all patients for PFS and OS. Post adjuvant durva, DCR was seen in 72.7%, CR of 54.5%. 1-year PFS was 71.5%, median PFS was 21.8 months. 1-year OS was 83.8%, median OS was 30.8 months. CR at 8 weeks post durvaRT was 62.5%. Node positive (N+) patients had similar median PFS and OS. DurvaRT was well tolerated. Grade ≥3 treatment-related adverse events: anemia, high lipase/amylase, immune-nephritis, transaminitis, dyspnea (grade 4-COPD/immune), fatigue, rash, diarrhea and scleritis. No difference in outcome was observed with PD-L1 status of baseline tumor. Patients with CR/PR or SD had an increase in naïve CD4 T cells, a decrease in PD-1+CD4 T cells at baseline and an increase in cytokine-producing CD8 T cells, including interferon gamma (IFNγ) producing cells, in the peripheral blood.
Durva with RT followed by adjuvant durva was safe with promising efficacy in localized BC patients with comorbidities, including N+ patients. Larger randomized studies, like S1806 and EA8185, are needed to evaluate the efficacy of combining immunotherapy and RT in BC.
NCT02891161.
Journal for immunotherapy of cancer. 2023 Feb [Epub]
Monika Joshi, Leonard Tuanquin, Junjia Zhu, Vonn Walter, Todd Schell, Matthew Kaag, Deepak Kilari, Jiangang Liao, Sheldon L Holder, Hamid Emamekhoo, Alexander Sankin, Suzzane Merrill, Hong Zheng, Joshua Warrick, Ralph Hauke, Benjamin Gartrel, Mark Stein, Joseph Drabick, David J Degraff, Yousef Zakharia
Department of Medicine, Penn State Cancer Institute, Hershey, Pennsylvania, USA ., Department of Radiation Oncology, Penn State Cancer Institute, Hershey, Pennsylvania, USA., Public Health Sciences, Penn State Cancer Institute, Hershey, Pennsylvania, USA., Microbiology and Immunology, Penn State Cancer Institute, Hershey, Pennsylvania, USA., Department of Surgery, Penn State Milton S Hershey Medical Center, Hershey, Pennsylvania, USA., Department of Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin, USA., Department of Medicine, Penn State Cancer Institute, Hershey, Pennsylvania, USA., Department of Medicine, University of Wisconsin-Madison Carbone Cancer Center, Madison, Wisconsin, USA., Department of Urology, Montefiore Medical Center, Bronx, New York, USA., Pathology, Penn State Health Milton S Hershey Medical Center, Hershey, Pennsylvania, USA., Nebraska Cancer Specialists, Omaha, Nebraska, USA., Department of Medicine, Columbia University/Herbert Irving Cancer Center, New York, New York, USA., Department of Pathology, Penn State College of Medicine, Hershey, Pennsylvania, USA., Department of Medicine, University of Iowa Holden Comprehensive Cancer Center, Iowa City, Iowa, USA.
PubMed http://www.ncbi.nlm.nih.gov/pubmed/36822667