Minimal Patient-Reported Side Effects for a Chemoablative Gel (UGN-102) Used as Frontline Treatment in Adults with Nonmuscle-Invasive Bladder Cancer

Abstract

Purpose:Optima II (“OPTimized Instillation of Mitomycin for Bladder Cancer Treatment,” clinicaltrials.gov: NCT03558503) was a phase 2b trial evaluating a nonsurgical alternative as a primary treatment for nonmuscle‐invasive bladder cancer (NMIBC). Patients received 6 weekly instillations of UGN-102, a mitomycin-containing reverse thermal gel. This is the first study to report on patient-reported side effects of UGN-102.Materials and Methods:Sixty-three patients enrolled in Optima II from 20 sites. Of these 63 patients, 44 were in the cohort completing a quarterly patient-reported outcome measure assessing side effects. Changes in side effects were evaluated using the Wilcoxon signed-rank test. Associations of 3-month outcomes with demographic and clinical characteristics were examined with regression, controlling for baseline values. Ten of 44 patients (23%) were interviewed after the trial to understand tolerability for future patients making treatment decisions. Transcripts were double-coded using standard methods.Results:In the patient-reported outcome measure cohort (44), 61% were men, 57% aged 65+ years and 89% were non-Hispanic White. UGN-102 did not cause decrements in patient-reported urinary symptoms, bloating/flatulence or malaise at the primary endpoint of 3 months. Sexual function mildly worsened. Future health worries improved. Demographics were not correlated with changes. Clinically, sexual function was correlated with new NMIBC and bloating/flatulence was associated with transurethral resection of bladder tumor within 12 months. In interviews, patients appreciated a nonsurgical alternative, would recommend the gel to other patients and would choose the gel over surgery.Conclusions:A nonsurgical, chemoablative gel (UGN-102) used as a primary treatment for NMIBC offers a more patient-centered therapeutic approach than standard treatments.

Injectable Thermoresponsive Hydrogels for Cancer Therapy: Challenges and Prospects

“…Jelymyto ® has since been registered for a clinical trial to assess its efficacy and safety in recurrent patients who already received the drug for upper tract urothelial carcinoma; however, the study was withdrawn due to a lack of participants, owing to the rarity of the disease [135]. Another clinical trial was recently completed for the thermosensitive mitomycin in nonsurgical primary chemoablation of nonmuscle invasive bladder cancer [136,137]. The system remained durable and achieved significant recovery with no reoccurrence within one year in 65% of the patients [136].…”

Novel Delivery Mechanisms for Existing Systemic Agents and Emerging Therapies in Bladder Cancer

“…Clinical trials have since transitioned to the evaluation of TC-3 hydrogel for low-grade or high-grade NMIBC prior to TURBT (NCT02307487) in a phase II dose escalation with results pending [ 54 ]. study Optima II (OPTimized Instillation of Mitomycin for Bladder Cancer Treatment) is a phase IIb single-arm clinical trial to evaluate a six-treatment induction course of the mitomycin reverse-thermal gel UGN-102 for the treatment of low-grade NMIBC at intermediate risk of recurrence [ 51 , 55 ]. Of 63 patients who received at least 1 instillation of UGN-102, the complete response (CR) rate was 65% with durable response (95% disease-free at 6 months and 63% remained disease-free at 12 months) [ 51 ].…”

“…Additionally, it should be noted that majority of patients (90%) completed all 6 induction instillations and only 10% discontinued treatment due to an adverse event [ 51 ]. Recently published interim results on patient-reported outcomes suggest that UGN-102 did not cause decrements in patient-reported symptoms at 3 months with the exception of mildly worsened sexual function, which resolved by 6 months [ 55 ].…”

Primary Chemoablation for Intermediate-risk Low-grade Bladder Cancer: New Paradigm or Added Uncertainty?

“…In addition, patient-reported outcomes as measured via the EORTC-QLQ-NMIBC24 (European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Non-muscle Invasive Bladder Cancer patients) were not worsened when compared to baseline in either the experimental or control arms, largely corroborating the patient-reported side effect profile of the phase 2b Optima II (OPTimized Instillation of Mitomycin for Bladder Cancer Treatment, clinicaltrials.gov: NCT03558503) UGN-102 study. 3 While the authors conclude that primary nonsurgical chemoablation with UGN-102 warrants further investigation, several features of the trial design and end point designation suggest the need for cautious interpretation of the study results before altering existing management paradigms.…”