ASCO 2024: Important Developments in Genitourinary Cancers

Important advances in genitourinary oncology presented at the ASCO 2024 Annual Meeting offer developments that could transform treatment protocols. This article reviews some of the meeting's key studies.

Efficacy of Nivolumab Combined with Gemcitabine and Cisplatin

The CheckMate 901 Trial: This randomized, open-label phase 3 study characterizes complete responders receiving nivolumab plus gemcitabine-cisplatin versus gemcitabine-cisplatin alone in metastatic urothelial carcinoma with lymph-node-only metastases. Initial data, presented at ESMO 2023 and published in the New England Journal of Medicine, showed significant improvements in progression-free survival (PFS) and overall survival with the combination (Abstract 4509).

Results: Complete response rates were 21.7% in the experimental group and 11.8% in the control group. Of complete responders, 52% had lymph-node-only metastases. Gemcitabine-cisplatin plus nivolumab reduced progression or death risk by 62% and death risk by 42%. Median overall survival was 46.3 months in the experimental group and 24.9 months in the control group.

Assessment of Enfortumab Vedotin Plus Pembrolizumab

The EV-302 Trial: This study demonstrated the superiority of enfortumab vedotin plus pembrolizumab over chemotherapy in locally advanced or metastatic urothelial carcinoma.

Results: Alongside improved survival, the combination improved quality of life and functioning. Significant improvements were reported in pain progression and severity. Compared with platinum-based chemotherapy, it improved not only survival but also patients' quality of life and function (Abstract 4502).

Efficacy of Trastuzumab Deruxtecan

The DESTINY-PanTumor02 Study: This study evaluated trastuzumab deruxtecan in HER2-positive solid tumors arising in tissues and organs. In the bladder cancer subgroup, treatment produced an objective response rate of 39% and a median response duration of 8.7 months (Abstract 4565).

Results: In this study of 41 patients, at a median follow-up of 12.6 months, the objective response rate was 39%, median PFS was 7 months and median response duration was 8.7 months. Grade 3 or higher drug-related adverse events occurred in 41.5%. Interstitial lung disease or pneumonitis occurred in approximately 4 patients. The objective response rate in the HER2 3+ group was 56.3%.

Prostate Cancer: Quality-of-Life Effects in EMBARK

The EMBARK Study: This study assessed how PSA-guided treatment interruption affected health-related quality of life with enzalutamide plus leuprolide in nonmetastatic castration-sensitive prostate cancer. EMBARK is a phase 3 randomized, placebo-controlled study in nonmetastatic castration-sensitive prostate cancer with high-risk biochemical recurrence (rising PSA). An important feature was interruption of treatment in responders after a specified period, according to PSA levels. PSA was assessed at week 37. Patients Who Had Undergone Radical Prostatectomy: Treatment was restarted when PSA rose above 2 ng/ml. Patients Who Had Not Undergone Radical Prostatectomy: Treatment was restarted when PSA rose above 5 ng/ml (Abstract 5005).

Results: Treatment interruption led to clinically meaningful improvements in responders. Sexual activity improved markedly with enzalutamide plus leuprolide. Treatment was interrupted in 90.9% receiving the combination, 85.9% receiving enzalutamide alone and 67.8% receiving leuprolide alone. Quality of life improved significantly after interruption in these patients. EMBARK showed positive effects of PSA-guided treatment interruption on health-related quality of life in responders, suggesting a potential role in improving quality of life during prostate cancer treatment. 

Baseline ctDNA Analysis in Metastatic Castration-Resistant Prostate Cancer

The PSMAfore Study: This phase 3 randomized study compares 177Lu-PSMA-617 with a change in androgen receptor pathway inhibitor (ARPI) in metastatic castration-resistant prostate cancer (mCRPC). Baseline samples were assessed for circulating tumor DNA (ctDNA) fraction and alterations in key prostate cancer driver genes (AR, TP53, PTEN). A ctDNA fraction >1% was associated with shorter radioactive progression-free survival (rPFS) and lower PSA50 and RECIST response rates in both the 177Lu-PSMA-617 and ARPI-switch arms. These gene alterations were also associated with poorer clinical outcomes regardless of treatment arm (Abstract 5008).

Conclusion: PSMAfore showed that a high ctDNA fraction or alterations in AR, TP53 and PTEN were associated with poorer outcomes in mCRPC. ctDNA fraction and genetic alterations may therefore be important biomarkers of response and progression and may guide future clinical decisions.

Kidney Cancer: Metastatic Chromophobe Renal Cell Carcinoma

Retrospective Analysis: Differences between first-line options were assessed in metastatic chromophobe renal cell carcinoma. Targeted doublet regimens provided longer survival than single-agent treatments (Abstract 4512).

Results: The study included 99 patients. Doublets containing a targeted agent produced a 52% lower treatment-failure risk and a 44% lower death risk than single-agent treatment. With an immunotherapy-containing doublet, median time to treatment failure was 15 months and median overall survival was 56 months.

Pembrolizumab and Platinum-Based Chemotherapy in Advanced Penile Cancer

The HERCULES Study: This study evaluated pembrolizumab plus platinum-based chemotherapy as first-line treatment for advanced penile squamous cell carcinoma (Abstract 5009).

Results: The combination produced an objective response rate of 39.4% and a favorable safety profile. High tumor mutational burden and HPV16 positivity emerged as potential markers of treatment effectiveness.

Conclusion

These studies presented at the ASCO 2024 Annual Meeting represent important progress in expanding options for genitourinary cancers and improving quality of life. Such advances are important steps toward optimizing treatment worldwide.