Advances in Prostate, Kidney and Bladder Cancer: ASCO GU 2024

The ASCO GU Cancers Symposium, organized by the American Society of Clinical Oncology (ASCO), covers prostate, bladder, kidney and testicular cancers within the field of genitourinary (GU) cancers . It is one of the most important meetings for sharing the latest developments in this field. Usually held in January or February, it brings together oncology specialists, researchers, physicians and healthcare professionals from around the world.

Here are some important research findings presented at the ASCO GU Cancers Symposium 2024. The most notable studies included:

• The BRCAAway study: Two treatment approaches are compared in patients with metastatic castration-resistant prostate cancer (mCRPC). One is sequential treatment, for example using one medicine and then switching to another. The other is combining several medicines at the initial treatment stage.
• The CheckMate-9ER and CheckMate-214 trials: These two studies in patients with clear-cell renal cell carcinoma (ccRCC) investigate the effectiveness of different treatments. Updated results examine new treatment combinations and their effects on patients.
• The retrospective mUC study: This study examines FGFR2 and FGFR3 mutations in patients with metastatic urothelial cancer (mUC). This retrospective study uses real-world data to assess treatment outcomes and effectiveness in patients with these specific genetic alterations.

These studies contribute substantially to knowledge in the field by examining new approaches and treatment outcomes in advanced prostate and kidney cancers.

The Growing Importance of Testing HDR in Prostate Cancer

BRCAAway addresses important questions about sequencing versus upfront combination treatment in mCRPC. In this phase 2 trial, patients with mCRPC who had not previously received PARP inhibitors, ARPIs or chemotherapy in the mCRPC setting carried homologous recombination repair mutations . Patients were randomized to abiraterone monotherapy at 1000 milligrams once daily, olaparib monotherapy at 300 milligrams twice daily, or the combination of abiraterone and olaparib. The primary endpoints assessed patients' treatment response using RECIST 1.1 criteria to track changes in tumor size, the prostate cancer-specific Prostate Cancer Working Group 3 criteria, physicians' overall clinical observations and patients' survival status. Together, these four assessment methods were used to measure treatment effectiveness comprehensively.

Secondary endpoints included response rates in measurable disease, PSA response and toxicity. This was a relatively small trial, with 21 patients in the combination arm, 19 in the abiraterone monotherapy arm and 21 in the olaparib monotherapy arm. Of the patients, 26% had received docetaxel chemotherapy in the hormone-sensitive setting, and only 3% had previously received an ARPI (darolutamide or enzalutamide, or in the nonmetastatic CRPC setting).

The results were particularly interesting. Median progression-free survival in the combination arm was 39 months , compared with 8.4 months in the abiraterone arm and 14 months in the olaparib arm. Importantly, crossover was allowed in the monotherapy arms: 8 of the 19 patients receiving abiraterone switched to olaparib, and 8 of the 21 patients receiving olaparib crossed over to abiraterone. Following randomization, both crossover groups had a median progression-free survival (PFS) of 16 months, a striking comparison with the 39 months among patients who began treatment with abiraterone plus olaparib.

These results are even more important given that only half of patients with mCRPC receive second-line treatment in real-world practice. They suggest that intensification with an ARPI plus a PARP inhibitor in first-line mCRPC offers greater effectiveness than sequencing these agents.

Which Biopsy Approach Is Best: Transperineal or Transrectal?

Studies comparing transperineal and transrectal biopsy are attracting attention in prostate cancer care. Abstract 261 is entitled "Randomized Trial of Transperineal Versus Transrectal Prostate Biopsy: Preventing Infectious Complications". This multicenter randomized study compared the two approaches in patients with suspected prostate cancer. No infections were reported with the transperineal approach, compared with 4 infections using the transrectal approach (p-value 0.059). Other complication rates were similarly low in both groups. Clinically significant cancer detection was also similar between the techniques, leading to the conclusion that the transperineal approach may reduce infection risk based on these findings.

Another study, abstract 273, entitled "Differences in Detecting High-Risk Prostate Cancer Between Transrectal and Transperineal Approaches", found that MRI fusion-based transperineal biopsy detected high-risk prostate cancer and other risk factors, such as perineural or lymphovascular invasion and cribriform patterns, at higher rates than the transrectal approach. These findings suggest that the transperineal approach is becoming increasingly important and may offer greater benefits than traditional methods.

New Treatment Approaches in Kidney Cancer

In kidney cancer, LITESPARK-005 and the CheckMate 9ER and CheckMate 214 trials stand out. Abstract 361 from LITESPARK-005 addresses patient-reported outcomes with belzutifan. This phase 3 trial examined belzutifan in patients with advanced or metastatic clear-cell renal cell carcinoma that had progressed after prior immune checkpoint and antiangiogenic treatments. At a median follow-up of 25.7 months, median treatment duration was 7.6 months with belzutifan versus only 3.9 months with everolimus. At the second interim analysis cutoff, 22.6% of patients remained on belzutifan, compared with only 5% on everolimus. Standardized quality-of-life questionnaires showed significantly longer time to deterioration in several scores with belzutifan than with everolimus. Patients in the everolimus arm also had worse physical functioning scores.

Longer-term follow-up from CheckMate 9ER and CheckMate 214 is also of interest. Abstract 362 from CheckMate 9ER showed that nivolumab plus cabozantinib significantly improved PFS and overall survival compared with sunitinib. At a median follow-up of 55 months, the combination was reported to reduce the risk of progression or death by 42% and the risk of death by 23% versus sunitinib. These results support its use as first-line treatment for advanced or metastatic renal cell carcinoma.

Using Enfortumab Vedotin and Erdafitinib

Two exciting abstracts from the UNITE database stand out in bladder cancer treatment. Abstract 537 is entitled "Outcomes in Patients with Advanced Urethral Carcinoma Treated with Enfortumab Vedotin After Avelumab in the UNITE Study". It reports outcomes for 49 patients who received third-line enfortumab vedotin after developing resistance to platinum-based treatment and avelumab maintenance. At a median follow-up of 8.5 months, median progression-free survival with enfortumab vedotin was 7 months, median overall survival was 13.3 months and the objective response rate was 54%. The study indicates that enfortumab vedotin is an effective salvage regimen for patients whose disease progressed on earlier lines of treatment.

Another study, abstract 616, entitled "Sequencing Erdafitinib and Enfortumab Vedotin in Patients with Metastatic Urothelial Cancer", examines the use of erdafitinib and enfortumab vedotin. Erdafitinib is a fibroblast growth factor receptor kinase inhibitor approved for patients with locally advanced or metastatic urothelial carcinoma carrying FGFR3 alterations after progression on one line of systemic treatment. This retrospective study reported outcomes with erdafitinib after enfortumab vedotin, erdafitinib before enfortumab vedotin, or enfortumab vedotin alone in patients with metastatic urothelial carcinoma and FGFR2 or FGFR3 alterations. Interestingly, patients who received both agents had longer overall survival than those receiving enfortumab vedotin alone, regardless of treatment sequence (hazard ratio 0.52). The objective response rate with enfortumab vedotin monotherapy was 49%, whereas in sequential treatment its objective response rate was 32% after erdafitinib and 67% before erdafitinib.

Although these are real-world data, the findings highlight the need for larger prospective studies, particularly on enfortumab vedotin after erdafitinib and its use as first-line treatment. These studies demonstrate important advances in bladder cancer care and promising options for patients.