Dr Schmidt on FDA-Approved Bladder-Sparing Therapies in BCG-Refractory NMIBC

“The challenges with [nogapendekin alfa inbakicept], up until very recently, have been the BCG shortage. [This drug requires] coadministration of BCG. If you don’t have BCG, it’s hard to use this drug right now, but they’re working on providing recombinant BCG with it, so I think that’ll increase the uptake of this treatment.”

Bogdana Schmidt, MD, MPH, an assistant professor in the Division of Urology at the University of Utah Huntsman Cancer Institute, highlighted bladder-sparing therapies FDA approved for the treatment of patients with BCG-refractory non–muscle-invasive bladder cancer (NMIBC).

Over the past 5 years, the BCG-refractory NMIBC space has seen 3 FDA approvals, Schmidt began. First, she noted that pembrolizumab (Keytruda) was approved in January 2020 for the treatment of patients with BCG-unresponsive, high-risk NMIBC and carcinoma in situ (CIS) with or without papillary tumors who are ineligible for or elected not to undergo surgery. With a role in the treatment paradigm for a variety of solid tumors, pembrolizumab is a familiar treatment among providers, she said. Pembrolizumab demonstrated initial promise, specifically in patients with intense urinary symptoms who would not benefit from intravesical treatments, she explained. Nevertheless, she emphasized that the associated systemic adverse effects need to be carefully considered in this patient population. Although it’s a great option to have in the treatment armamentarium, it's often not everyone’s first choice, she added.

In December 2022, the FDA approved nadofaragene firadenovec-vncg (Adstiladrin) for the treatment of patients with high-risk BCG-unresponsive NMIBC and CIS with or without papillary tumors. Notably, it was the first adenoviral vector–based gene therapy approved in this setting, Schmidt explained.

Furthermore, in April 2024, the FDA approved nogapendekin alfa inbakicept-pmln (Anktiva) plus BCG for the treatment of patients with BCG-unresponsive NMIBC and CIS with or without papillary tumors, she continued. The mechanism of action further stimulates the response to BCG, particularly in this population of patients with BCG-refractoriness, she explained. However, she emphasized that this treatment modality has faced a challenge regarding the recent BCG shortage, especially because BCG is required in combination with nogapendekin alfa inbakicept. Recombinant BCG could soon be an option to help increase the uptake of the treatment, Schmidt concluded.