AUA 2022: A Phase II Study of Check Point Inhibitor, Durvalumab (MEDI4736) for Bacillus Calmette-Guerin Unresponsive Carcinoma in Situ of the Bladder

(  The 2022 Annual Meeting of the American Urological Association was host to a moderated poster session for non-invasive bladder cancer. Dr. Roger Li presented the results of a phase II trial evaluating Durvalumab in patients with BCG-unresponsive CIS of the bladder.

Given the shortage of treatment options in the BCG-unresponsive NMIBC disease space, there has been intensified research efforts to development treatment strategies with durable responses. Radical cystectomy remains the gold standard treatment option in this disease space, but many patients are either unfit or unwilling to undergo such a morbid procedure. In this study, the authors sought to investigate the efficacy of a PD-L1 inhibitor, Durvalumab, in the treatment of BCG-unresponsive CIS.

This study was a single center, open label, phase two trial of patients with BCG-unresponsive CIS of the bladder. Enrolled patients received IV Durvalumab 1500 mg IV q4 weeks for a total of 12 months. Patients underwent a cystoscopy every 3 months during the initial 12-month administration period, with for cause biopsies as indicated. During the second 12 months, cystoscopy was performed every 4 months. Patients were taken off study if disease persistence or progression to invasive disease occurred. The primary study endpoint was CR as determined by a 6 month mapping biopsy. Duration of complete response and recurrence-free survival were secondary endpoints. Pre- and post-treatment PD-L1 status was determined by the SP263 assay. Adverse events were captured using CTCAE v4.03.

Seventeen patients were enrolled and began durvalumab for BCG-unresponsive CIS. Median patient age was 77.0 years (IQR 69.0-79.0). CIS alone was present in 13 (76.5%) patients. The median number of prior BCG instillations was 12. 4 patients were excluded from the study after they were found to have persistent HG NMIBC on 3 month bladder biopsies. Among the remaining 13 patients who were disease free at 3 months, only 3 (18%) had a 6-month CR with a median duration of response of 14 months.

Progression to muscle invasive or metastatic disease occurred in 3 (18%) patients and 9 (53%) underwent a radical cystectomy. No correlation was observed between PD-L1 expression and clinical response to durvalumab. Grade 1-2 treatment-related adverse events occurred in 11 patients with the most frequent being fatigue (35%), diarrhea (18%), pancreatic enzyme elevation (12%), rash (6%), and hypothyroidism (6%).
 Dr. Li concludes that immune checkpoint inhibition with durvalumab in BCG-unresponsive CIS demonstrates a favorable safety profile, albeit with a modest CR rate. Further research ein in a larger cohort is needed to determine the efficacy and safety profile of immune check point inhibitors in this disease space.

Presented By: Roger Li, MD, Assistant Professor, Urologic Oncology, Moffitt Cancer Center, Tampa, FL

Written By: Rashid Sayyid, MD, MSc – Urology Chief Resident, Augusta University/Medical College of Georgia, @rksayyid on Twitter during the 2022 American Urological Association (AUA) Annual Meeting, New Orleans, LA, Fri, May 13 – Mon, May 16, 2022.