Dr Lotan on Ongoing Research With Novel Agents in BCG-Unresponsive NMIBC

Yair Lotan, MD, professor, urology, chief, urologic oncology, Jane and John Justin Distinguished Chair in Urology, UT Southwestern Harold C. Simmons Comprehensive Cancer Center; medical director, Urology Clinic, UT Southwestern and Parkland Health and Hospital System, discusses ongoing research with novel agents in patients with Bacillus Calmette-Guérin (BCG)–unresponsive non–muscle-invasive bladder cancer (NMIBC).

Several agents are under investigation in clinical trials in this patient population, many of which may receive FDA approval in the future. First, the phase 2b SunRISe-1 trial (NCT04640623) is evaluating TAR-200, which uses a novel drug delivery system that facilitates the sustained release of gemcitabine directly into the bladder. The device is inserted and removed cytoscopically and is replaced every 3 weeks during the first 6 months of treatment. In data presented during the 

, the complete response (CR) rate was 83.5% (95% CI, 74%-91%) with TAR-200 monotherapy, and the estimated 12-month duration of response rate was 65.7% (95% CI, 45.2%-80.1%).

In cohort A of the single-arm, phase 2 KEYNOTE-057 trial (NCT02625961), at 3 months, the CR rate was 41% with pembrolizumab monotherapy in patients with high-risk disease without carcinoma in situ. Regarding a phase 3 trial (NCT02773849) investigating nadofaragene firadenovec-vncg (Adstiladrin), at 3 months, the CR rate with this agent was 53.4%. At 1 year, the CR rate was 45.5%. Additionally, in cohort A of the phase 2/3 QUILT-3.032 trial (NCT03022825), at a median follow-up of 23.9 months, the rate of CR at any time with nogapendekin alfa inbakicept-pmln (Anktiva; N-803) plus BCG was 71% (95% CI, 59.6%-80.3%). Finally, for those enrolled in the phase 3 BOND-003 trial (NCT04452591), the rate of CR at any time with cretostimogene grenadenorepvec monotherapy was 75.2% (95% CI, 65%-83%), and responses were durable, Lotan explains.

Lastly, the phase 1/2 LEGEND trial (NCT04752722) is evaluating the intravesical therapy EG-70 in patients with high-risk, BCG-unresponsive NMIBC. The phase 1 portion of this trial is complete, and the phase 2 portion is ongoing, he notes. Early data from this trial have shown promising responses with EG-70, and response durability data will help determine whether this agent should join the NMIBC treatment paradigm, Lotan concludes.

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Yair Lotan, MD, discusses ongoing research with novel agents in patients with BCG-unresponsive non–muscle-invasive bladder cancer.

Yair Lotan, MD, discusses factors informing treatment selection for patients with BCG-unresponsive non-muscle invasive bladder cancer.  

Dr Lotan on Factors Informing Treatment Selection in BCG-Unresponsive NMIBC

Yair Lotan, MD, professor, urology, chief, Urologic Oncology; Jane and John Justin Distinguished Chair in Urology, UT Southwestern Medical Center; medical director, Urology Clinic, UT Southwestern, Parkland Health and Hospital System, discusses factors informing treatment selection for patients with Bacillus Calmette–Guérin (BCG)–unresponsive non-muscle invasive bladder cancer (NMIBC).

Balancing the associated adverse effects and potential efficacy of treatments against the associated risks is a crucial part of the conversation between oncologists and patients, particularly when discussing treatment options for bladder cancer, Lotan begins. The ultimate decision rests with the patient and depends on several factors, including age, comorbidities, surgical risks, and life expectancy, he emphasizes. For example, a patient with a longer life expectancy might opt for a more aggressive treatment with a higher cure rate, even if it comes with a greater morbidity risk, Lotan says.

The presence of disease invasion also plays a key role in treatment decision-making, Lotan continues. Patients with T1 disease that has invaded the lamina propria face a higher risk of disease progression compared with those who have noninvasive disease confined to the mucosa, Lotan states. He adds that the presence of invasive disease may prompt patients to consider more aggressive interventions. Additionally, the decision-making process can be influenced by the natural history of the disease and the patient’s overall prognosis, he notes.

Another factor that affects treatment selection is the response to initial treatment, Lotan adds. If a patient’s disease recurs after they have received noninvasive therapeutic options, they may need to reconsider their treatment plan, he explains. In some cases, patients initially resist more aggressive treatments, such as bladder removal, but after multiple unsuccessful attempts with other therapies, they may ultimately opt for surgery, Lotan says. Ongoing disease evaluation supports personalized, evolving treatment discussions that adapt to patients’ changing circumstances and preferences, he concludes.

Yair Lotan, MD, discusses factors informing treatment selection for patients with BCG-unresponsive non-muscle invasive bladder cancer.

Yair Lotan, MD

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Dr Lotan on Ongoing Research With Novel Agents in BCG-Unresponsive NMIBC

Dr Lotan on Factors Informing Treatment Selection in BCG-Unresponsive NMIBC