NMIBC | Image Credit: 
© Sebastian Kaulitzki -
stock.adobe.com

Patients receiving the gemcitabine intravesical system (Inlexzo, formerly TAR-200) for the treatment of BCG-unresponsive, high-risk non–muscle invasive bladder cancer (NMIBC) achieved high complete response (CR) rates and favorable responses regarding disease progression and radical cystectomy rates, according to data from the phase 2bs SunRISe-1 trial (NCT04640623).

Data from SunRISe-1 were previously published in the 

. That report showed a CR rate of 82% (95% CI, 72 to 90) in patients with BCG-unresponsive NMIBC with CIS receiving gemcitabine intravesical system monotherapy. Further, 51% of patients remained in CR for at least 1 year.

For the current study, which was presented at the 

025 Society of Urologic Oncology Annual Meeting

, the investigators, led by Christopher M. Pieczonka, MD, chief executive officer and director of Clinical Research for Associated Medical Professionals in New York, presented data on recurrence, progression, and time to cystectomy in patients receiving gemcitabine intravesical system monotherapy (cohort 2).

Findings showed that at a median follow-up for cohort 2 of 20.2 months (range, 2-48 months), investigators reported an 82.4% CR rate with gemcitabine intravesical system monotherapy; 70 of 85 patients achieved a CR. Of the 70 patients with a CR, 37 (52.9%) had a DoR of 12 months or longer. In addition, at the clinical cut-off, 37 responders remain in complete response; 33 were reported as ongoing with no event, and 4 were permanently censored due to study discontinuation or receipt of subsequent therapy.

The investigators also detailed recurrence and progression, as well as time to radical cystectomy. Forty-one (48.2%) of the 85 patients experienced disease persistence, progression, or recurrence. Thirty (42.9%) of these patients were initial responders. Of the 41 patients, the majority were reported to have persistence or recurrence of high-risk NMIBC. Seven (8.2%) patients progressed to T2 or higher disease. Eighteen (21.2%) of the 85 patients received a radical cystectomy; 12 (14.1%) of these patients were responders. The median time to cystectomy was not estimable, and estimated radical cystectomy-free rates were 86.6% (95% CI, 76.6-92.6) at 12 months and 75.5% (95% CI, 63.4-84.1) at 24 months. Seven deaths unrelated to study treatment were reported.

[Gemcitabine intravesical system] monotherapy is associated with a high CR rate and durable responses, with minimal risk of disease progression to a more advanced (T2 or higher) disease stage. The low rate of RC [radical cystectomy] in cohort 2 of SunRISe-1 highlights that [gemcitabine intravesical system] treatment may result in potential delay to RC,” the authors wrote in their poster.

SunRISe-1 included adult patients with histologically confirmed high-risk NMIBC carcinoma in situ (with or without papillary disease), ECOG performance status of 0 to 2, persistent or recurrent disease within 12 months of completing BCG, and who were unresponsive to BCG and not undergoing radical cystectomy. A population of patients with papillary-only high-risk NMIBC (no CIS) were also included; these patients received gemcitabine intravesical system monotherapy (cohort 4). The rest of the population was randomly assigned to gemcitabine intravesical system plus cetrelimab (cohort 1), gemcitabine intravesical system monotherapy (cohort 2), and cetrelimab monotherapy (cohort 3). The gemcitabine intravesical system was administered every 3 weeks for the first 24 weeks, and then every 12 weeks through week 96. For cohorts 1 to 3, the primary end point was overall CR rate, and key secondary end points included duration of response (DoR), overall survival, safety, and tolerability. For cohort 4, the primary end point was disease-free survival.

The investigators reported that 85 patients with CIS had received gemcitabine intravesical system monotherapy as of March 31, 2025. Median age was 71 years (range, 40-88 years), and 68 (80.0%) were male.

Pieczonka CM, Daneshmand S, Van der Heijden MS, et al. Gemcitabine intravesical system (TAR-200) monotherapy in Bacillus Calmette-Guérin–unresponsive high-risk non–muscle-invasive bladder cancer: characterization of recurrence, progression, and time to cystectomyPresented at: Society of Urologic Oncology Annual Meeting; December 2-5, 2025; Phoenix, Arizona. Abstract 140. 

Daneshmand S, Heijden MSV, Jacob JM, et al. TAR-200 for Bacillus Calmette-Guérin-unresponsive high-risk non-muscle-invasive bladder cancer: Results from the phase IIb SunRISe-1 study. 

. 2025:101200JCO2501651. doi:10.1200/JCO-25-01651

Articles

The gemcitabine intravesical system demonstrated high complete response (CR) rates in patients with BCG-unresponsive, high-risk non–muscle invasive bladder cancer (NMIBC) in the SunRISe-1 trial. At a median follow-up of 20.2 months, 82.4% of patients achieved CR, with 52.9% maintaining CR for at least 12 months. Disease persistence, progression, or recurrence occurred in 48.2% of patients, with 8.2% progressing to T2 or higher disease. Radical cystectomy rates were low, with 21.2% undergoing the procedure. The trial design included multiple cohorts, focusing on CR rate and duration of response.

Gemcitabine intravesical system in BCG-unresponsive, high-risk NMIBC led to high CR rates and low radical cystectomy rates.

Gemcitabine Intravesical System Yields Low Rate of Radical Cystectomy in BCG-Unresponsive, High-Risk NMIBC

Hormone-Sensitive Prostate Cancer
| Image Credit: © Sebastian Kaulitzki 
– stock.adobe.com

Data from a subgroup analysis of the phase 3 ARANOTE trial (NCT04736199) demonstrate that darolutamide (Nubeqa) and androgen deprivation therapy (ADT) was associated with an improvement in radiographic progression-free survival (rPFS) and other efficacy end points vs placebo plus ADT in Black patients with metastatic hormone-sensitive prostate cancer/

2025 American Urological Association Annual Meeting

In ARANOTE, patients starting on ADT were randomly assigned 2:1 to receive darolutamide 600 mg daily or placebo. The primary end point was rPFS. Time to metastatic castration-resistant prostate cancer, time to prostate-specific antigen (PSA) progression, proportion of patients reaching a PSA level lower than 0.2 ng/mL at any time, time to initiation of subsequent anticancer therapy, and safety were secondary end points.

ARANOTE included 669 patients, of whom 65 were Black. Forty-one of these patients received darolutamide and 24 received placebo. The investigators reported that the baseline characteristics were “similar between treatment arms and generally consistent with the overall ARANOTE population, except Black patients had higher median baseline PSA levels (99.6 ng/mL vs 21.3 ng/mL) and a greater proportion had high-volume mHSPC (78.5% vs 70.6%),” the investigators wrote in their poster.

“With regards to our substudy that encompassed the Black population, it's very important to understand that we had about 10% of the ARANOTE population that self-identified as Black," lead study author Quoc-Dien Trinh, MD, MBA, said. "We know that representation of minorities in clinical trials is a problem in general, but specifically in the space of metastatic prostate cancer, so these results are definitely interesting. What we found was that Black patients do relatively well from an efficacy standpoint and from a safety standpoint with ADT plus darolutamide.” Trinh is the chair of urology at the University of Pittsburgh School of Medicine and chair of urology at the University of Pittsburgh in Pennsylvania.

The investigators reported that treatment with darolutamide reduced the risk of radiological progression or death by 49% in Black men. Regarding the primary end point of rPFS, the HR for Black patients was 0.51 compared with 0.57 in the overall ARANOTE cohort.

“[Regarding] PSA suppression to less than 0.2 ng/mL, we found that nearly 60% of Black men achieved suppression with ADT plus darolutamide vs less than 20% on the ADT alone arm, so a three-fold difference,” Trinh said.

Regarding safety, the investigators reported that treatment-emergent adverse event incidence was similar between the treatment groups for Black patients and was similar to what was seen in the overall ARANOTE population. In addition, the median duration of treatment in Black patients was 22.6 months in the darolutamide group vs 17.3 months in the placebo group.

Discussing the significance of the substudy, Trinh commented, “I think this is a very important study, but also a very important type of analysis to conduct, whether it's ARANOTE or any other study, which is to look at subpopulations; in this case, Black men. We know that Black men are more likely to develop prostate cancer, but also to die from prostate cancer. So it is very reassuring to know that in this subpopulation, the outcomes and the efficacy of this drug were certainly similar, and [there was] perhaps some signal that it could be even more beneficial. That, in itself, is very interesting. The other very important thing is that we know there is a lot of real-world evidence suggesting that underserved populations are less likely to get the latest therapies, sometimes more likely to get ADT alone, and sometimes the conversations and the things we may hear pertains to the fact that perhaps intensification leads to potentially more [adverse events], and assessing the safety of this drug in this population is very important, and the findings, again, were very reassuring. So the message to clinicians and to patients is that treatment intensification with darolutamide is certainly something that should be strongly considered in light of our substudy.”

Trinh Q-D, George DJ, Shore N, et al. Efficacy and safety of darolutamide plus androgen-deprivation therapy in Black patients with metastatic hormone-sensitive prostate cancer from the phase 3 ARANOTE trial. 

 2025;213(5S):e578. doi:10.1097/01.JU.0001109908.15997.76.01

The phase 3 ARANOTE trial demonstrated that darolutamide combined with androgen deprivation therapy (ADT) significantly improved radiographic progression-free survival (rPFS) and other efficacy endpoints in Black patients with metastatic hormone-sensitive prostate cancer compared to placebo plus ADT. The study included 65 Black patients, with 41 receiving darolutamide. Results showed a 49% reduction in the risk of radiological progression or death. Nearly 60% of Black men achieved PSA suppression with darolutamide, compared to less than 20% with ADT alone. Safety profiles were consistent across treatment groups.

Darolutamide plus ADT improved rPFS in Black patients with metastatic hormone-sensitive prostate cancer treated in ARANOTE.

Subgroup Data From ARANOTE Highlight rPFS Benefit of Darolutamide Plus ADT in Black Patients With mHSPC

Prostate Cancer | Image Credit:
© Sebastian Kaulitzki – stock.adobe.com

Treatment with the combination of enzalutamide (Xtandi) and leuprolide acetate or placebo plus leuprolide acetate led to full testosterone recovery after suspension of treatment at 36 weeks in patients with prostate cancer, according to a post hoc analysis of the phase 3 EMBARK trial (NCT02319837).

 in Las Vegas, Nevada, by Stephen J. Freedland, MD, professor of urology at Cedars-Sinai in Los Angeles, California.

“One of the unique aspects of EMBARK was that after 9 months of treatments, PSA [prostate-specific antigen] was measured, and if patients got a really good PSA response—less than 0.2 [ng/mL]—treatment was suspended. We know ongoing castration/low testosterone levels can impact quality of life and lead to other poor outcomes. The question was, how quickly does testosterone recover? What percent of people ultimately do recover their testosterone, and particularly as a function of age, because we know that older patients have a slower time to recovery. The purpose of this post hoc analysis was to look at the kinetics of testosterone recovery during the off-treatment cycle,” Freedland said in his presentation.

EMBARK enrolled patients with prostate cancer who had high-risk biochemical recurrence. Patients had a screening PSA level of at least 1 ng/mL after radical prostatectomy or at least 2 ng/mL above the nadir for primary external beam radiation therapy, had a PSA doubling time of 9 months or less, no metastases on bone scan or CT/MRI, and a testosterone level of at least 150 ng/dL. The primary end point was metastasis-free survival (MFS) by blinded independent central review (BICR) for enzalutamide plus leuprolide acetate vs leuprolide acetate alone. Secondary end points included MFS by BICR for enzalutamide monotherapy vs leuprolide acetate alone, time to PSA progression, time to first use antineoplastic therapy, and overall survival. Safety was an additional secondary end point.

Patients were randomly assigned 1:1:1 to enzalutamide plus leuprolide acetate, placebo plus leuprolide acetate, and enzalutamide monotherapy. At 36 weeks, if a patient’s PSA level was lower than 0.2 ng/mL, treatment was suspended. Testosterone levels were measured every 12 weeks. “Normal” testosterone was defined as greater than 175 ng/mL. In his presentation, Freedland explained that the EMBARK study entry criterion was a testosterone level of at least 150 ng/dL.

Freedland reported that the median time to first occurrence of testosterone recovery to greater than 175 ng/dL was 8.3 months (range, 0-36.0 months) in the enzalutamide plus leuprolide acetate arm vs 5.9 months (range, 0-47.1 months) in the placebo plus leuprolide arm. Mean time to first occurrence of testosterone recovery to greater than 175 ng/dL was 8.9 months (± SD=5.0) in the enzalutamide plus leuprolide acetate arm vs 8.0 months (± SD=5.1) in the placebo plus leuprolide arm. More than 80% of patients in both groups had a full recovery of testosterone, and more 98% of patients had at least partial recovery. Two percent or fewer had no recovery of testosterone.

The investigators stratified their findings by men younger than 70 and men 70 years of age or older. In the enzalutamide plus leuprolide acetate group, the median time to first occurrence of testosterone recovery to greater than 175 ng/dL was 8.3 months (range, 0-36.0 months) in men younger than 70 and 8.3 months (range, 1.9-30.4 months) in men 70 years of age or older. In the placebo plus leuprolide acetate group, the median time to first occurrence of testosterone recovery to greater than 175 ng/dL was 5.7 months (range, 2.8-24.8 months) in men younger than 70 and 8.1 months (range, 0-47.1 months) in men 70 years of age or older. Eighty-nine percent and 92% of patients younger than 70 years of age achieved full recovery of testosterone in the enzalutamide plus leuprolide acetate vs placebo plus leuprolide acetate group, respectively.

“Importantly, no patients in the younger age group had no recovery at all,” Freedland noted.

Seventy-eight percent and 84% of patients 70 years of age or older achieved full recovery of testosterone in the enzalutamide plus leuprolide acetate vs placebo plus leuprolide acetate group, respectively.

“In summary, what we showed is EMBARK, for those who got to the treatment suspension— which was the majority of patients—that with time, the testosterone recovers…and the vast majority of patients…do ultimately develop return of testosterone,” Freedland said in his concluding remarks.

Freedland SJ, Tutrone R, Saad F, et al. Testosterone recovery following treatment suspension of enzalutamide plus leuprolide or leuprolide alone in patients with high-risk biochemically recurrent prostate cancer: embark post hoc analysis. 

. 2025;213(5S):e506. doi:10.1097/01.JU.0001109880.25183.6b.03

The EMBARK trial evaluated testosterone recovery in prostate cancer patients after treatment suspension with enzalutamide plus leuprolide acetate or placebo plus leuprolide acetate. The study found that over 80% of patients experienced full testosterone recovery, with a median recovery time of 8.3 months for the enzalutamide group and 5.9 months for the placebo group. Age influenced recovery time, with younger patients recovering faster. The trial highlighted the potential for testosterone recovery post-treatment, which is crucial for improving quality of life and reducing adverse outcomes associated with prolonged low testosterone levels.

The majority of patients with prostate cancer treated with an enzalutamide or leuprolide acetate regimen recovered their testosterone levels.

Patrick Campbell

Articles

Gemcitabine Intravesical System Yields Low Rate of Radical Cystectomy in BCG-Unresponsive, High-Risk NMIBC

Subgroup Data From ARANOTE Highlight rPFS Benefit of Darolutamide Plus ADT in Black Patients With mHSPC

Leuprolide Acetate With Enzalutamide or Placebo Is Associated With Full Testosterone Recovery in Prostate Cancer