(UroToday.com) The 2024 SUO annual meeting included a urothelial carcinoma session, featuring a presentation by Dr. Sia Daneshmand discussing safety and tolerability of TAR-200 monotherapy in patients with BCG-unresponsive high risk non muscle invasive bladder cancer (NMIBC) in SunRISE-1. Treatment options that are safe, bladder preserving, and effective for patients with BCG-unresponsive high risk NMIBC are limited.
TAR-200, a novel targeted releasing system, is designed to provide sustained release of gemcitabine in the bladder over many days. SunRISe-1 (NCT04640623) is an ongoing, phase 2b study assessing the efficacy and safety of TAR-200 + cetrelimab (Cohort 1), TAR-200 alone (Cohort 2), or cetrelimab alone (Cohort 3) in patients with BCG-unresponsive high risk NMIBC ineligible for or refusing radical cystectomy. TAR-200 alone is also being assessed in patients with papillary disease only (Cohort 4). At AUA 2024, preliminary results showed a promising complete response rate of 83% and durable responses in patients with BCG-unresponsive high risk NMIBC treated with TAR-200. At SUO 2024, Dr. Daneshmand and colleagues reported additional results on the safety and tolerability of TAR-200 monotherapy in Cohort 2.
Patients aged ≥18 years with histologically confirmed CIS ± papillary disease (high-grade Ta, any T1), ECOG performance status of 0-2, and persistent or recurrent high risk NMIBC with last dose of BCG ≤12 months prior to CIS diagnosis were eligible for Cohort 1-3:
TAR-200 was dosed every 3 weeks through Week 24, then every 12 weeks until week 96. The primary end point of the SunRISe-1 trial is complete response rate at any time, and secondary end points reported included duration of response, safety, and tolerability.
As of May 13, 2024, 85 patients with CIS (median age, 71 years; range, 40-88; concomitant papillary disease, 32.9%) received TAR-200 monotherapy:
The centrally assessed complete response rate was 83.5 (71/85), and the investigator assessed complete response rate was 85.9% (73/85):
TAR-200 insertion success rate was 98.8%, and the median indwelling duration was 22 days (range: 5-26). Overall, 71 of 85 patients (83.5%) reported treatment-related adverse events. The majority of treatment-related adverse events were grade 1-2 lower urinary tract symptoms. The most common treatment-related adverse events (≥10%) were pollakiuria (38.8%), dysuria (35.3%), urinary tract infection (20.0%), micturition urgency (17.6%), and hematuria (14.1%). The median duration of all treatment-related adverse events that had recovered/resolved was 22 days (IQR, 8-112):
There were 8 patients (9.4%) that had grade 3-4 treatment-related adverse events, 5 (5.9%) had serious treatment-related adverse events, and no treatment related deaths occurred:
Five patients (6%) had treatment-related adverse events that led to treatment discontinuation; these included noninfective cystitis (n = 3; 1 grade 1, 2 grade 2), pollakiuria (n = 1, grade 2), and urinary retention (n = 1, grade 2), within 4.8 months of starting treatment.
Dr. Daneshmand concluded his presentation discussing safety and tolerability of TAR-200 monotherapy in patients with BCG-unresponsive NMIBC in SunRISE-1 with the following take home messages:
- TAR-200 monotherapy was well tolerated in SunRISe-1, with a high rate of insertion success and a median indwelling duration of 22 days
- Commonly reported lower urinary tract related treatment related adverse events were manageable and resolved after a short duration
- TAR-200 has a promising safety and efficacy profile as a local, bladder-sparing treatment in high risk NMIBC unresponsive to BCG
- These results support the continued investigation of TAR-200 in BCG-unresponsive high risk NMIBC
Presented by: Siamak Daneshmand, MD, Professor of Urology, University of Southern California, Los Angeles, CA
Written by: Zachary Klaassen, MD, MSc – Urologic Oncologist, Associate Professor of Urology, Georgia Cancer Center, Wellstar MCG Health, @zklaassen_md on Twitter during the 2024 Society of Urologic Oncology (SUO) Annual Meeting, Dallas, TX, Tues, Dec 3 – Fri, Dec 6, 2024.