Highlights of Novel Therapies Under Study in Genitourinary Cancers

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Here are some brief reports from the 2023 ASCO Genitourinary (GU) Cancers Symposium that we hope are of interest. They include real-world evidence about the use of avelumab maintenance in metastatic urothelial carcinoma, data on the feasibility of sequencing radium-223 and Lu-177–PSMA-617 in metastatic castration-resistant prostate cancer, and disappointing results comparing atezolizumab monotherapy vs chemotherapy in the first-line treatment of metastatic urothelial carcinoma.

Avelumab Maintenance Therapy in Metastatic Urothelial Carcinoma

Patients in the general population with advanced/metastatic urothelial cancer treated with avelumab switch maintenance after responding to or having stable disease on first-line platinum-based chemotherapy had baseline characteristics, treatment patterns, and responses to first-line induction chemotherapy similar to prior studies, according to retrospective ‘real-world’ data from the -PATRIOT-II study.1 The ongoing study will continue to evaluate real-world outcomes and treatment patterns for switch maintenance avelumab, explained lead author Petros Grivas, MD, PhD, Professor and Clinical Director of the Genitourinary Cancers Program at the University of Washington and Fred Hutchinson Cancer Center, Seattle.

Petros Grivas, MD, PhD

Petros Grivas, MD, PhD

At baseline, among 160 patients treated with first-line platinum-based chemotherapy prior to avelumab switch maintenance therapy, 13% had a complete response, and 68% had a partial response. A total of 11% had stable disease, and response was unknown in 8% of patients. Almost two-thirds of patients (62.5%) received cisplatin-based chemotherapy, and 37.5% of patients received carboplatin-based chemotherapy. The median number of chemotherapy cycles was five, and the median duration of platinum-based chemotherapy was 13 weeks.

Avelumab was approved by the U.S. Food and Drug Administration in June 2020 for locally advanced or metastatic urothelial cancer that had not progressed on first-line platinum-based chemotherapy, based on data from the phase III JAVELIN Bladder 100 trial.2

“We wanted to corroborate the findings of the JAVELIN Bladder 100 trial with ‘real-world’ (off trial) data. To describe ‘real-world’ evidence of what is happening in clinical practice, we designed the PATRIOT-II study,” Dr. Grivas explained.

The ongoing retrospective PATRIOT-II study collected data from 37 geographically dispersed oncology practices for 160 patients treated with platinum-based chemotherapy who then went on to avelumab switch maintenance.

The median patient age was 70, and 77% were male. Most patients (90%) were White; 3% were Black, 3% were Asian, and 4% were Hispanic. A total of 64% of patients were current or former smokers, and 78% had no known family history of bladder cancer. In addition, 76% had Eastern Cooperative Oncology Group performance status of 0 or 1. Among the 48% of patients tested for PD-L1 status, 28% had PD-L1–positive disease, and 21% had PD-L1–negative disease.

Avelumab switch maintenance therapy was initiated at a median of 4 weeks after the completion of platinum-based chemotherapy, and most patients (81%) started at the standard dose of 800 mg once every 2 weeks.

Future analyses will examine treatment patterns, real-world clinical outcomes, and health-care resource utilization at 6 and 12 months after baseline data collection.

“In the future, we’re going to focus more on the actual outcomes with avelumab switch maintenance therapy [overall survival, progression-free survival]. This retrospective study will give us interesting data on how the implementation of avelumab maintenance looks in ‘real-world’ (off trial) practice setting,” Dr. Grivas said.

Sequencing Radiotherapies in Metastatic Prostate Cancer

Use of lutetium Lu-177–prostate-specific membrane antigen–617 (Lu-177–PSMA-617) after radium-223 was safe and well tolerated in patients with metastatic castration-resistant prostate cancer. Overall survival was similar regardless of the time of initiation of Lu-177–PSMA-617—whether it was within 6 months or more than 6 months after completing treatment with radium-223—according to retrospective data from the RALU trial.3

“The rationale for the RALU study is that radium-223 and Lu-177–PSMA-617 have both demonstrated overall survival benefit and acceptable safety in patients with metastatic castration-resistant prostate cancer,” said Kambiz Rahbar, MD, of the Department of Nuclear Medicine, University Hospital of Münster, Germany. “The question RALU set out to answer is whether it is safe to sequence two radionuclide therapies, an alpha emitter and a beta emitter, in patients with metastatic castration-resistant prostate cancer.”

Kambiz Rahbar, MD

Kambiz Rahbar, MD

The study analyzed outcomes from patients with metastatic castration-resistant prostate cancer who were treated with Lu-177–PSMA-617 within 6 months of radium-223 treatment (group 1; n = 42) and those who were treated with Lu-177–PSMA-617 at least 6 months after radium-223 treatment (group 2; n = 90). Visceral metastasis was present in 24% of patients in group 1 and 29% of patients in group 2 before undergoing therapy with Lu-177–PSMA-617.

A total of 40% of group 1 and 64% of group 2 had four or more prior therapies, with all patients having received prior radium-223 treatment. The most common additional therapies were abiraterone (60% in group 1 and 77% in group 2), enzalutamide (50% in group 1 and 78% in group 2), docetaxel (71% in group 1 and 76% in group 2), and cabazitaxel (17% in group 1 and 26% in group 2).

Between the start of Lu-177–PSMA-617 therapy to 30 days after the last dose, 71% and 82% of patients in groups 1 and 2, respectively, experienced any-grade treatment-related adverse events; the most common events were fatigue (12% and 7%, respectively), nausea (12% and 8%), and dry mouth (7% and 18%). Grade 3 or 4 treatment-related adverse events, excluding laboratory abnormalities, were observed in 36% of patients in group 1 and 24% of patients in group 2.

Treatment-related deaths occurred in 2% of patients in group 1 and 4% of patients in group 2. Treatment-related adverse events leading to dose delays were reported in 10% and 9% of patients in groups 1 and 2, respectively.

There was no statistically significant difference in median overall survival between groups 1 and 2. In group 1, median overall survival from the start of Lu-177–PSMA-617 treatment was 12.0 months, and it was 13.2 months in group 2. During therapy with Lu-177–PSMA-617, prostate-specific antigen responses of 50% or more were observed in 53% of patients in group 1 and 39% of patients in group 2.

“In conclusion, we can say these data show that treating patients with lutetium within 6 months of completing radium was clinically feasible and well tolerated,” Dr. Rahbar said.

Atezolizumab Monotherapy for Untreated Advanced Urothelial Cancer

Atezolizumab monotherapy did not improve overall survival compared with placebo plus platinum-based chemotherapy in patients with untreated locally advanced or metastatic urothelial cancer, according to findings from an exploratory analysis of the phase III IMvigor130 trial.4 However, the data from this analysis suggest that atezolizumab may be of benefit in patients whose tumors have high PD-L1 expression, particularly in cisplatin-ineligible patients.

Aristotelis Bamias, MD, PhD

Aristotelis Bamias, MD, PhD

“Data from this final overall analysis of the IMvigor130 study of first-line atezolizumab in metastatic urothelial cancer were generally consistent with the findings from the first and second interim overall survival analyses. Exploratory efficacy data suggest a clinical benefit with atezolizumab monotherapy as first-line treatment for cisplatin-ineligible patients with PD-L1 IC2/3 metastatic urothelial cancer,” said lead author Aristotelis Bamias, MD, PhD, Professor at the National and Kapodistrian University of Athens.

The trial enrolled patients with locally advanced or metastatic urothelial cancer who had not received prior systemic therapy in the metastatic setting. Patients were randomly assigned 1:1:1 to receive atezolizumab plus platinum (cisplatin or carboplatin) and gemcitabine (arm A), atezolizumab alone (arm B), or placebo plus platinum and gemcitabine (arm C). The co-primary endpoints of the trial were investigator-assessed progression-free and overall survival for arm A vs arm C in the intention-to-treat population and overall survival for arm B vs arm C in the intention-to-treat and PD-L1 IC2/3 populations.

According to the hierarchical statistical design of the study, since no significant advantage in favor of arm A over arm C was found in the final overall survival analysis, the survival analysis for arms B vs C was exploratory. The median overall survival was 15.2 months in the atezolizumab arm (n = 360) vs 13.3 months in the chemotherapy arm (n = 359). The 12- and 24-month overall survival rates with atezolizumab were 57.9% and 34.5% vs 54.6% and 32.3% with chemotherapy, respectively.

In further exploratory analyses, survival data showed an advantage for atezolizumab in patients with higher PD-L1 expression. Median overall survival was 27.5 months with atezolizumab (n = 88) vs 16.7 months with chemotherapy (n = 85) in patients with PD-L1 IC2/3. Patients with PD-L1 IC0/1 had median overall survival of 13.5 months with atezolizumab (n = 272) vs 12.9 months with chemotherapy (n = 274).


For more on the use of atezolizumab in urothelial cancer from the IMvigor130 trial, see an interview with Aristotelis Bamias, MD, PhD, on The ASCO Post Newsreels at

The benefit of atezolizumab in cisplatin-ineligible patients with PD-L1 IC2/3 expression was more robust, according to the investigators. Median overall survival was 18.6 months with atezolizumab (n = 50) vs 10.0 months with chemotherapy (n = 43). Cisplatin-ineligible patients with PD-L1 IC0/1 expression had median overall survival of 11.2 months with atezolizumab (n = 140) vs 11.8 months with chemotherapy.

Regarding safety, no new signals were reported with additional follow-up. “Overall, the tolerability profile of atezolizumab monotherapy was favorable relative to that of placebo plus chemotherapy,” Prof. Bamias said. “The benefit-risk ratio of atezolizumab vs chemotherapy supports atezolizumab as first-line treatment for cisplatin-ineligible patients with PD-L1 IC2/3 metastatic urothelial cancer,” he concluded.

Of note, atezolizumab was voluntarily withdrawn from the U.S. market in November 2022 for a first-line indication in metastatic urothelial cancer. 

DISCLOSURE: Dr. Grivas has served as a consultant or advisor to 4D Pharma, Aadi Bioscience, Asieris Pharmaceuticals, Astellas Pharma, AstraZeneca, BostonGene, Bristol Myers Squibb, CG Oncology, Dyania Health, Exelixis, Fresenius Kabi, G1 Therapeutics, Genentech, Gilead Sciences, Guardant Health, ImmunityBio, Infinity Pharmaceuticals, Janssen, Lucence, Mirati Therapeutics, MSD, Pfizer, PureTech, Regeneron, Roche, Seattle Genetics, Silverback Therapeutics, Strata Oncology, QED Therapeutics, Merck KGaA, and UroGen Pharma; and has received institutional research funding from Bavarian Nordic, Bristol Myers Squibb, Clovis Oncology, Debiopharm Group, G1 Therapeutics, Gilead Sciences, GlaxoSmithKline, Mirati Therapeutics, MSD, Pfizer, QED Therapeutics, and Merck KGaA. Dr. Rahbar has received honoraria from Advanced Accelerator Applications and Bayer; and has served as a consultant or advisor to ABX Advanced Biochemical Compounds, Advanced Accelerator Applications, and Bayer. Prof. Bamias has received honoraria from Astellas Pharma, Bristol Myers Squibb, Debiopharm Group, MSD, and Sanofi; has served as a consultant or advisor to AstraZeneca, Bristol Myers Squibb, Ferring, Ipsen, MSD, Pfizer, and Roche; and has received institutional research funding from AstraZeneca, Bristol Myers Squibb, Ipsen, Pfizer, and Roche.


1. Grivas P, Barata PC, Moon H, et al: Baseline characteristics from a retrospective, observational, US-based, multicenter, real-world study of avelumab first-line maintenance in locally advanced/metastatic urothelial carcinoma (PATRIOT-II). 2023 ASCO GU Cancers Symposium Abstract 465. Presented February 17, 2023.

2. U.S. Food and Drug Administration: FDA approves avelumab for urothelial carcinoma maintenance treatment. June 30, 2020. Available at Accessed March 14, 2023.

3. Rahbar K, Essler M, Eiber M, et al: Time interval between radium-223 therapy and lutetium-177–prostate-specific membrane antigen treatment and outcomes in the RALU study. 2023 ASCO GU Cancers Symposium. Abstract 73. Presented February 16, 2023.

4. Bamias A, Davis ID, Galsky MD, et al: Final overall survival analysis of atezolizumab monotherapy vs chemotherapy in untreated locally advanced or metastatic urothelial carcinoma from the phase 3 IMvigor130 study. 2023 ASCO GU Cancers Symposium. Abstract LBA441. Presented February 17, 2023.