Gomella details evolving treatment paradigm in NMIBC

Urology Times JournalVol 49 No 04
Volume 49
Issue 04

At the 2021 New York GU 14th Annual Interdisciplinary Prostate Cancer Congress® Leonard G. Gomella, MD, FACS, chairman of the Department of Urology at the Sidney Kimmel Cancer Center, discussed the current state of the treatment paradigm in non-muscle invasive bladder cancer (NMIBC) and highlighted novel agents emerging on the horizon.1


The management of NMIBC starts with the resection of all visible disease, with a focus on the existing standard of care, intravesical Bacillus Calmette–Guérin (BCG), for patients with this disease, according to Gomella.

“Non-muscle invasive bladder cancer management is something commonly encountered by urologists,” Leonard G. Gomella, MD, FACS, chairman of the Department of Urology at the Sidney Kimmel Cancer Center, explained in his presentation. “Initial management [is to] resect all visible disease and think about enhanced cystoscopy as a way to complete that process. If [the disease is] high-grade, consider intravesical BCG therapy; [and with] low-volume, just usually do follow-up cystoscopy.”

The standard approach utilized by most care providers for BCG intravesical immunotherapy is known as the SWOG protocol, in which patients receive an initial 6-weekly induction dose, followed by 3 weekly doses at 3 months and every 6 months following initial treatment for up to 2 or 3 years.

Along with a robust response, BCG therapy is typically well tolerated. Some common adverse events associated with BCG treatment include fever, hematuria, and granulomatous prostatitis.

While BCG is the current standard of care for NMIBC, BCG failures do exist. Specifically, recurrence and progression can happen with treatment via BCG, with 1- and 5-year recurrence rates of 15% to 61% and 31%to 78%, respectively. As for progression, the 1- and 5-year rates are up to 17% and up to 45%, respectively. These existing data strengthen the need for additional therapeutic options for patients with this disease.2

“There’s no question that BCG is probably the best-known immuno-oncology agent,” explained Gomella. “In reality, we’ve been using BCG for bladder cancer certainly since the FDA approval way back in 1990, and it’s really become the standard of care for non-muscle invasive bladder cancer.”

After BCG failure

Among patients who are eligible for BCG, data suggests up to 40% may not respond to treatment or will become refractory to BCG. For high-risk patients who fit this description, Gomella explains that radical cystectomy should be considered as the first option. If patients are unwilling to undergo cystectomy or prefer another therapy, Gomella continued to say that intravesical chemotherapy, among other therapies, represent an option although noting its limited success.

For intravesical chemotherapy, monotherapy treatment is less efficacious than BCG, with paclitaxel, docetaxel, doxorubicin, epirubicin, and valrubicin (Valstar) among the drugs utilized in this treatment. Gomella noted that valrubicin is the only drug that has received FDA approval for this indication.

More, systemic pembrolizumab (Keytruda) to treat patients with BCG-refractory bladder cancer was recently approved by the FDA in response to data from the phase 2 KEYNOTE-057 study (NCT02625961).3,4

The median duration of response was 12.7 months (range, 0.0+ to 20.5+ months), with 75% of patients experiencing a complete response duration of 6 or more months and 53% of patients showing a complete response duration of 9 or more months.

“If you have a high-grade BCG failure, valrubicin and systemic pembrolizumab currently are the FDA approved salvage medications,” concluded Gomella. “Again, cystectomy should always be considered and at least presented to the patient.”

Emerging agents

Several investigational agents are generating excitement in the field. The FDA granted a priority review designation to the protein-fusion drug Vicineum (VB4-845) in February 2021 for the treatment of patients with high-risk, BCG-unresponsive NMIBC.5

The intravesical therapy nadofaragene firadenovec has shown promise in BCG-unresponsive NMIBC. In a phase 3 trial, the complete (CR) response rate with nadofaragene firadenovec was 53.4% at 3 months in patients with carcinoma in situ with or without concomitant high-grade Ta or T1 disease (CIS ± Ta/T1).6 The 12-month CR rate was 24.3% and the median duration of CR was 9.69 months. Further, 45.5% of patients with an initial CR, were still free of high-grade recurrence at 1 year.

Also of note, data from the phase 2/3 QUILT 3.032 study (NCT03022825) shared at the 2021 Genitourinary Cancers Symposium showed that the combination of N-803 (Anktiva), a novel interleukin-15 (IL-15) superagonist complex, and BCG achieved CRs in 71% (51/72) of patients with BCG-unresponsive, high-risk, non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS) with or without Ta or T1 disease.7


1. Gomella LG. Management of Non–Muscle-Invasive Bladder Cancer. Presented at: 14th Annual New York GU Congress. March 12-13, 2021.

2. Chang SS, Boorjian SA, Chou R et al. Diagnosis and treatment of non-muscle invasive bladder cancer: AUA/SUO guideline. J Urol. 2016;196(4):1021-1029. doi: 10.1016/j.juro.2016.06.049

3. FDA approves pembrolizumab for BCG-unresponsive, high-risk non-muscle invasive bladder cancer. FDA. January 8, 2020. Accessed March 12, 2021. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-pembrolizumab-bcg-unresponsive-high-risk-non-muscle-invasive-bladder-cancer

4. Balar AV, Kamat AM, Kulkarni GS, et al. Pembrolizumab (pembro) for the treatment of patients with Bacillus Calmette-Guérin (BCG) unresponsive, high-risk (HR) non–muscle-invasive bladder cancer (NMIBC): Over two years follow-up of KEYNOTE-057. J Clin Oncol. 2020;38(suppl 15):5041. doi: 10.1200/JCO.2020.38.15_suppl.5041

5. Sesen Bio Announces FDA Acceptance and Priority Review of its Biologics License Application for Vicineum. Posted online February 16, 2021. Accessed February 27, 2021. https://bwnews.pr/3rZcbi0

6. Boorjian SA, Alemozaffar M, Bad Konety BR, et al. Intravesical nadofaragene firadenovec gene therapy for BCG-unresponsive non-muscle-invasive bladder cancer: a single-arm, open-label, repeat-dose clinical trial [published online November 27, 2020]. Lancet Oncol. doi: 10.1016/S1470-2045(20)30540-4

7. Chamie K, Chang S, Gonzalgo M, et al. Phase II/III clinical results of IL-15RαFb superagonist N-803 with BCG in BCG-unresponsive non-invasive bladder cancer (NMIBC) carcinoma in-situ (CIS) patients (cohort A). J Clin Oncol. 2021;39(suppl 6):510. doi:10.1200/JCO.2021.39.6_suppl.510

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