Dr Daneshmand on Using TAR-200 to Address Unmet Needs in BCG-Unresponsive NMIBC

“Although BCG has been effective, there is a significant number of patients who don’t respond and need additional therapies. Several trials are addressing this, and there have been many FDA-approved therapies over the past few years, but TAR-200 fills in this [treatment gap] nicely for BCG-unresponsive disease.”

Sia Daneshmand MD, professor, urology, clinical scholar designation; director, Clinical Research, urologic oncology fellowship, Keck School of Medicine, University of Southern California, discusses how the incorporation of TAR-200 into the bladder cancer treatment armamentarium could uniquely address existing unmet needs for patients with high-risk, Bacillus Calmette-Guérin (BCG)–unresponsive non–muscle-invasive bladder cancer (NMIBC) with carcinoma in situ (CIS).

Treatment options for BCG-unresponsive NMIBC have remained limited for the past 2 decades, but the recent introduction of multiple new therapies into the treatment paradigm reflects an increasing focus on therapeutic development for this population, Daneshmand begins. Although BCG remains an effective treatment, a significant proportion of patients do not respond and require additional therapeutic strategies, he says. TAR-200 represents a potential advancement in this setting; it uses a novel drug delivery mechanism designed to enhance treatment efficacy, Daneshmand states.

Unlike conventional intravesical therapies that require drug instillation for 1 hour per session, TAR-200 is a drug/device combination that provides sustained intravesical delivery of gemcitabine over multiple days, Daneshmand explains. This prolonged exposure enhances drug penetration into the bladder tissue, potentially improving its effectiveness, he says. Preclinical studies have also demonstrated that active drug metabolites remain detectable in the bladder several days after administration, suggesting an extended dwell time that could contribute to increased efficacy, Daneshmand notes.

The initial focus of TAR-200 development has been in patients with CIS, a disease state that typically cannot be managed surgically, he continues, adding that demonstrating efficacy in this setting provides a clear assessment of the drug’s antitumor activity without confounding effects from surgical resection. Beyond CIS, TAR-200’s sustained drug release may also offer benefits in more invasive disease, such as T1 tumors, although this has not yet been established in clinical trials, Daneshmand notes.

Future research is needed to define TAR-200’s role in the broader NMIBC treatment paradigm, particularly in comparison with other emerging therapies and in combination with existing agents, he emphasizes. The potential for deeper tissue penetration and longer drug exposure could position TAR-200 as an important addition to the therapeutic paradigm for BCG-unresponsive disease, Daneshmand concludes.