Primary Chemoablation for Recurrent Low-Grade Intermediate-Risk NMIBC: The ENVISION Trial

In the first urothelial session at the Society of Urologic Oncology Annual Meeting, Sandip M. Prasad, MD, MPhil, presented the results of the ENVISION trial assessing the role of primary chemoablation in patients with recurrent low-grade intermediate risk (LG-IR) non-muscle invasive bladder cancer (NMIBC).

Dr. Patel began by highlighting the patient population included in this study. According to AUA/SUO NMIBC guidelines, patients with LG-IR NMIBC include those who have 1 or 2 of the following features: multifocality, tumor size greater than 3 centimeters, or early or frequent recurrences (defined as more than 1 recurrence within the first year of the current diagnosis). Current guidelines recommend repeated transurethral resection of bladder tumor (TURBT), with use of adjuvant chemotherapy. However, adherence to adjuvant therapy is relatively low in practice. Additionally, repeated TURBT is associated with significant morbidity. However, there is a lack of evidence for alternative approaches.

One such option may be UGN-102, a mitomycin-containing reverse thermal gel. This approach was previously investigated in 2 prior trials – the single arm phase 2b OPTIMA study and the phase 3 randomized ATLAS trial.

In the ENVISION study, the authors performed a phase 3, single arm, open label trial to evaluate the efficacy of UGN-102 in patients with LG-IR NMIBC. Following screening and enrolment, patients received an induction course of 6 once-weekly instillations prior to primary endpoint evaluation at 3 months. They subsequently had ongoing follow-up to 63 months.

The primary study outcome was the proportion of patients who achieved a complete response rate at 3-month evaluation. Secondary outcomes included duration of response out to 63 months, durable complete response rate, and disease-free survival. There was additional safety analysis examining the incidence of treatment-emergent adverse events (TRAEs), serious TRAEs, TRAEs of special interest, and the presence of abnormal clinical laboratory test results.

Dr. Patel highlighted that this study cohort of 240 patients had characteristics that we would expect: median age was 70 years and 61% were men. Nearly all (96%) had undergone prior TURBT while only 9.2% had more than 2 prior episodes of LG NMIBC. Nearly all patients (95%) were able to successfully receive 6 instillations.

In terms of the primary outcome, he demonstrated that a complete response was seen in 190 patients, representing 79.2% of the study cohort (95% CI 73.5-84.1%). Among the 50 patients who did not have a complete response, 35 (14.6%) had residual disease, 6 (2.5%) had progression to high grade disease, 4 patients had indeterminate evaluation, and 5 had missing outcome data.

Within the first 3 months after treatment, treatment related adverse events of any grade were seen in 127 (52.9%) patients. The majority of these were mild (n=60, 25%) or moderate (n=47, 19.6%) with 16 (6.7%) severe or medically significant, 2 (0.8%) life-threatening, and 2 (0.8%) death. Two serious adverse events were seen in the form of urethral stenosis and urinary retention. The 2 deaths were deemed un-related to study treatment (pneumonia and cardiac arrest).

Dr. Patel finished his presentation by concluding that the phase 3 ENVISION trial remains ongoing. Based on 3-month follow-up, 79% of patients achieved a complete response and the treatment was generally well tolerated with most adverse event being mild to moderate severity. Awaiting ongoing data assessing the secondary endpoint of duration of response, this treatment approach potentially represents the first, non-surgical treatment for patients with LG-IR NMIBC.