Breakthroughs in Bladder, Prostate, and Kidney Cancer: What Oncologists Need to Know From ASCO 2025
The 2025 American Society of Clinical Oncology (ASCO) Annual Meeting featured many exciting developments in the field of oncology. The Oncology Brothers— Rahul Gosain, MD, MBA, and Rohit Gosain, MD— hosted an Advancements in Oncology event featuring Enrique Grande, MD, PhD, MSc, of MD Anderson Cancer Center Madrid, and Petros Grivas, MD, PhD, of Fred Hutchinson Cancer Center, to discuss key advances in genitourinary oncology.
Bladder Cancer
Starting with recent advances in muscle-invasive bladder cancer (MIBC), Dr. Grivas highlighted the practice-changing nature of the phase 3 NIAGARA trial (NCT03732677) , noting the combination of cisplatin-based chemotherapy with durvalumab followed by radical cystectomy and adjuvant durvalumab as a new standard of care in the management of patients with MIBC.
Dr. Grivas further noted that even in patients with pathologic complete response (pCR), he would give adjuvant durvalumab based on the available data. However, he said he was eagerly awaiting an upcoming presentation at ASCO by Thomas Powles, MD, MBBS, MRCP, of Barts Cancer Institute on circulating tumor DNA (ctDNA) in patients with MIBC who received perioperative durvalumab in NIAGARA.
Dr. Grande noted that the regimen had not yet been approved in Europe and thus had not yet been implemented widely into clinical practice; however, he was looking forward to its adoption.
Of note, Dr. Powles presented the ctDNA data from NIAGARA in the subsequent days. He stated that ctDNA was strongly prognostic for the trial’s outcomes, and ctDNA clearance after neoadjuvant treatment was associated with improved event-free survival. He also noted that adding durvalumab to neoadjuvant chemotherapy increased the number of patients with ctDNA clearance by 13%.
Importantly, ctDNA-negative status was not associated with pCR, while ctDNA-positive status highly correlated with non-pCR. Furthermore, disease-free survival (DFS) was improved in patients who were ctDNA negative post cystectomy with the addition of durvalumab (hazard ratio [HR], 0.49; 95% CI, 0.28-0.84).
Dr. Grande then brought forward the importance of bladder preservation from a patient perspective and the need to uniformly define what a clinical complete response (cCR) entails, as well as whether achieving a cCR would allow a greater proportion of patients to undergo bladder preservation.
The discussion then shifted into the role of ctDNA and its possible clinical implications. Dr. Grande was asked whether he would continue durvalumab in a patient who is near completion of adjuvant therapy with the NIAGARA protocol and is ctDNA positive. Dr. Grande noted the trial was designed to complete 1 full year of treatment with immune checkpoint inhibitors (ICIs); thus, without additional data, one would likely stop therapy at that time and monitor the patient for signs of progression.
With regard to chemoradiation regimens for patients unable or unwilling to undergo radical cystectomy, Dr. Grivas noted that oncologists could choose from three options for radiosensitizing chemotherapy: weekly cisplatin, low-dose gemcitabine once or twice weekly, or fluorouracil and mitomycin C. Given the lack of prospective data comparing these regimens, he recommended picking the regimen one is most comfortable with.
Dr. Grivas reiterated the lack of data regarding the use of neoadjuvant chemotherapy prior to chemoradiation, although he noted that it may be helpful in certain situations and the field will continue to evolve, as will treatment approaches with the available data.
In the metastatic setting, Drs. Grande and Grivas discussed the profound impact of EV-302 trial ( NCT04223856 ), shifting the treatment paradigm to enfortumab vedotin plus pembrolizumab (EV-P) as the new standard of care for frontline treatment of metastatic disease.
Dr. Grande noted that EV-P had not been well studied in pure variant histologies; thus, these patients may not be ideal candidates to receive the regimen in the frontline setting. Drs. Grivas and Grande both said that severe baseline neuropathy would be another contraindication for treatment with EV-P. Dr. Grivas also mentioned severely impaired liver function (Child-Pugh class C or higher) and severe uncontrolled autoimmune conditions as additional contraindications.
The conversation surrounding bladder cancer concluded with a discussion on the question of ICI rechallenge in patients, given the incorporation of ICIs in earlier stages of disease. Dr. Grivas shared that he considers how well ICIs were initially tolerated and the time interval between completion of ICI treatment and disease recurrence.
In general, Dr. Grivas will consider ICI rechallenge if the time interval is greater than 6 months, although he emphasized a lack of prospective data makes this a very difficult topic to address.
Prostate Cancer
After reviewing updates in bladder cancer treatment, the panel discussed the anticipated oral presentation of the phase 3 AMPLITUDE clinical trial (NCT04497844), which was to be presented on the final day of ASCO (subsequent to this Oncology Brothers event).
This randomized trial evaluated the efficacy and safety of the PARP inhibitor niraparib with abiraterone acetate plus prednisone (AAP) compared with placebo versus abiraterone in patients with metastatic castration-sensitive prostate cancer (mCSPC) that harbor pathogenic somatic or germline alterations in genes for homologous recombination repair (HRR).
Patients with HRR mutations have a poorer prognosis compared with non-HRR patients in the mCSPC setting. The AMPLITUDE study was launched to provide new treatment options for this subset of patients and builds on prior efficacy data from phase 3 clinical trials of PARP inhibitors in patients with HRR mutations in the mCRPC setting. These trials include TALAPRO-2 (talazoparib, HRR mutated), PROpel (olaparib, BRCA1/2 mutated), and MAGNITUDE (niraparib, BRCA1/2 mutated).
Gerhardt Attard, MD, PhD, of University College London, presented the data from AMPLITUDE, which randomized 696 patients with germline or somatic HRR gene alterations (BRCA1, BRCA2, BRIP1, CDK12, CHEK2, FANCA, PALB2, RAD51B, RAD54L) to either niraparib plus AAP and androgen deprivation therapy (ADT) or placebo plus AAP and ADT. The niraparib combination regimen had a statistically significant improvement in radiographic progression-free survival (rPFS, the study’s primary end point). With a median follow-up of 30.8 months, the median rPFS was not reached for the niraparib plus AAP versus 29.5 months for the placebo-containing arm (HR, 0.63; 95% CI, 0.49-0.80; P = .0001).
Median overall survival (mOS) at the first interim analysis (after 193 of 389 events) showed numerically longer survival (HR, 0.79; 95% CI, 0.59-1.04; P = .10). However, these data are immature; additional survival data will emerge with ongoing follow-up.
The next question addressed the experts’ preferred choice of androgen receptor pathway inhibitor. Dr. Grande noted that, in Spain, insurance coverage plays a significant role in that decision, because abiraterone acetate is currently available as a generic medication and thus is more commonly covered by insurance. However, in situations where all agents are available (eg, covered by a patient’s insurance, willingness to pay for agents out of pocket), patient comorbidities and each drug’s adverse effect profile play significant roles in the choice of treatment, given limited direct comparisons and similar efficacy.
Dr. Grivas then addressed the optimal first-line agent in the mCRPC setting. He noted that Pluvicto (lutetium Lu 177 vipivotide tetraxetan) had been evaluated in patients after docetaxel therapy. Additional clinical trials are needed to determine the optimal first-line therapy. In his current clinical practice, many factors—such as radiographic findings on prostate-specific membrane antigen and FDG-PET scans, disease burden, prostate-specific antigen level, concern for neuroendocrine differentiation, patient comorbidities/performance status, and access to nuclear medicine practice—shape the decision on the sequence of agents used.
Renal Cell Carcinoma
The moderators and panelists acknowledged the presentation on updated survival data from the phase 3 KEYNOTE-564 (NCT03142334) trial, which randomized patients with clear-cell renal cell carcinoma (ccRCC) with high-risk features for metastatic recurrence to either adjuvant pembrolizumab for 1 year (every 3 weeks for about 17 cycles) or placebo.
Naomi Haas, MD, of the University of Pennsylvania, presented updated data from the fourth prespecified interim analysis, with a median of 69.5 months of patient follow-up. The median DFS was not reached in the pembrolizumab arm versus 68.3 months in the placebo arm (HR, 0.71; 95% CI, 0.59-0.86). The median OS was not reached in either arm (HR, 0.66; 95% CI, 0.48-0.90), with an estimated OS at the 5-year mark of 87.7% and 82.3% in the pembrolizumab arm and placebo arm, respectively.
The panelists were posed questions regarding the optimal first-line regimen, including the decision between ICI doublets (immuno-oncology agents)—specifically, nivolumab plus ipilimumab—versus ICI/ tyrosine kinase inhibitor (TKI) combinations (eg, lenvatinib plus pembrolizumab, axitinib plus pembrolizumab, and cabozantinib plus pembrolizumab).
Dr. Grande noted that all the options approved by the FDA are reasonable and worthy of discussion with patients. Dr. Grivas added that ongoing data for patients in the International Metastatic RCC Database Consortium (IMDC) favorable-risk category show higher long-term survival. These findings were highlighted in the final analysis of the phase 3 CheckMate 214 study (NCT02231749), presented by Dr. Robert Motzer, MD, of Memorial Sloan Kettering Cancer Center. With a median follow-up of 111 months, there was improved mOS with nivolumab plus ipilimumab compared with sunitinib in the intent-to-treat population (52.7 months vs 37.8 months; HR, 0.71; 95% CI, 0.62-0.82) and the IMDC intermediate/favorable risk population (HR, 0.69; 95% CI, 0.59-0.81).
Even in the favorable risk category, there was a trend toward higher survival (HR, 0.80; 95% CI, 0.59-1.09). Per Dr. Grivas, ICI/TKI combinations might be preferable in settings where rapid disease control and reduction in tumor burden are needed (eg, bulky symptomatic disease, tumor thrombus), but otherwise, dual ICI combinations might be preferred in hopes of achieving better long-term overall survival. In addition, dual ICI would be preferred for patients with tumors exhibiting sarcomatoid histology. In the absence of direct head-to-head comparison in the setting of a prospective clinical trial, Dr. Grivas could not advocate for one specific ICI/TKI combination.
In the question-and-answer segment, the role of oligo metastasectomy (including in the central nervous system) was posed to the genitourinary experts. Drs. Grande and Grivas agreed that this would be a case-by-case discussion with multidisciplinary input. One of the guiding principles involved understanding each individual’s clinical course (eg, rate of growth, sites of disease, response to treatment, and depth and duration of response) so that patients might gain the most clinical benefit from any intervention aimed at prolonging survival.