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Published online: 2024-04-08

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Advances in genitourinary cancer treatment after the 2023 ESMO congress

Dawid Sigorski12, Małgorzata Osmola34, Michał Wilk54

Abstract

The European Society of Medical Oncology (ESMO) congress is the leading oncological meeting during which the most essential clinical practice-changing data are unveiled. In this review, we would like to present the most clinically relevant data presented during the 2023 ESMO conference regarding genitourinary cancers, including the results of clinical trials with immune-checkpoint inhibitors, antibody-drug conjugates, radioligands, PARP inhibitors, and new therapeutic targets. The most clinically relevant studies include the EV-302 trial in bladder cancer, PSMAfore in prostate cancer, and LITESPARK-005 in kidney cancer. 

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References

  1. Galsky MD, Hahn NM, Rosenberg J, et al. Treatment of patients with metastatic urothelial cancer "unfit" for Cisplatin-based chemotherapy. J Clin Oncol. 2011; 29(17): 2432–2438.
  2. Fisher MD, Shenolikar R, Miller PJ, et al. Treatment Patterns and Outcomes in Stage IV Bladder Cancer in a Community Oncology Setting: 2008-2015. Clin Genitourin Cancer. 2018; 16(6): e1171–e1179.
  3. Bajorin DF, Dodd PM, Mazumdar M, et al. Long-term survival in metastatic transitional-cell carcinoma and prognostic factors predicting outcome of therapy. J Clin Oncol. 1999; 17(10): 3173–3181.
  4. Powles T, Park SeH, Voog E, et al. Avelumab Maintenance Therapy for Advanced or Metastatic Urothelial Carcinoma. N Engl J Med. 2020; 383(13): 1218–1230.
  5. Wysocki PJ, Chłosta P, Chrzan R, et al. Polish Society of Clinical Oncology and Polish Urological Association Guidelines for the diagnosis and treatment of renal cell cancer. Oncol Clin Pract. 2021; 16(6): 301–330.
  6. Galsky MD, Arija JÁ, Bamias A, et al. IMvigor130 Study Group. Atezolizumab with or without chemotherapy in metastatic urothelial cancer (IMvigor130): a multicentre, randomised, placebo-controlled phase 3 trial. Lancet. 2020; 395(10236): 1547–1557.
  7. Powles T, Csőszi T, Özgüroğlu M, et al. KEYNOTE-361 Investigators. Pembrolizumab alone or combined with chemotherapy versus chemotherapy as first-line therapy for advanced urothelial carcinoma (KEYNOTE-361): a randomised, open-label, phase 3 trial. Lancet Oncol. 2021; 22(7): 931–945.
  8. van der Heijden MS, Sonpavde G, Powles T, et al. CheckMate 901 Trial Investigators. Nivolumab plus Gemcitabine-Cisplatin in Advanced Urothelial Carcinoma. N Engl J Med. 2023; 389(19): 1778–1789.
  9. Maas M, Stühler V, Walz S, et al. Enfortumab vedotin - next game-changer in urothelial cancer. Expert Opin Biol Ther. 2021; 21(7): 801–809.
  10. Bellmunt J, de Wit R, Fradet Y, et al. Randomized phase III KEYNOTE-045 trial of pembrolizumab versus paclitaxel, docetaxel, or vinflunine in recurrent advanced urothelial cancer: results of >2 years of follow-up. Ann Oncol. 2019; 30(6): 970–976.
  11. Powles TB, Valderrama BP, Gupta S, et al. LBA6 EV-302/KEYNOTE-A39: Open-label, randomized phase III study of enfortumab vedotin in combination with pembrolizumab (EV+P) vs chemotherapy (Chemo) in previously untreated locally advanced metastatic urothelial carcinoma (la/mUC). Ann Oncol. 2023; 34: S1340.
  12. McGregor BA, Sonpavde GP, Kwak L, et al. The Double Antibody Drug Conjugate (DAD) phase I trial: sacituzumab govitecan plus enfortumab vedotin for metastatic urothelial carcinoma. Ann Oncol. 2024; 35(1): 91–97.
  13. Siefker-Radtke AO, Necchi A, Park SeH, et al. BLC2001 Study Group, BLC2001 Study Group. Erdafitinib in Locally Advanced or Metastatic Urothelial Carcinoma. N Engl J Med. 2019; 381(4): 338–348.
  14. Siefker-Radtke AO, Matsubara N, Park SH, et al. THOR cohort 2 investigators. Erdafitinib versus pembrolizumab in pretreated patients with advanced or metastatic urothelial cancer with select FGFR alterations: cohort 2 of the randomized phase III THOR trial. Ann Oncol. 2024; 35(1): 107–117.
  15. Ghoneim MA, Abdel-Latif M, el-Mekresh M, et al. Radical cystectomy for carcinoma of the bladder: 2,720 consecutive cases 5 years later. J Urol. 2008; 180(1): 121–127.
  16. Huguet J. Follow-up after radical cystectomy based on patterns of tumour recurrence and its risk factors. Actas Urol Esp. 2013; 37(6): 376–382.
  17. Sridhar S, O'Donnell PH, Flaig TW, et al. 2365MO Study EV-103 cohort L: Perioperative treatment w/ enfortumab vedotin (EV) monotherapy in cisplatin (cis)-ineligible patients (pts) w/ muscle invasive bladder cancer (MIBC). Ann Oncol. 2023; 34: S1203.
  18. Necchi A, Bedke J, Galsky M, et al. Phase 3 KEYNOTE-905/EV-303: Perioperative pembrolizumab (pembro) or pembro + enfortumab vedotin (EV) for muscle-invasive bladder cancer (MIBC). J Clin Oncol. 2023; 41(6_suppl): TPS585–TPS585.
  19. Thibault C, Bennamoun M, Flechon A, et al. 2364MO Durvalumab (D) +/- tremelimumab (T) in combination with dose-dense MVAC (ddMVAC) as neoadjuvant treatment in patients with muscle-invasive bladder carcinoma (MIBC): Results of NEMIO, a randomized phase I-II trial. Ann Oncol. 2023; 34: S1202.
  20. Szabados BE, Martinez EN, Marquez FJA, et al. 2363MO A phase II study investigating the safety and efficacy of neoadjuvant atezolizumab in non-urothelial, muscle invasive bladder cancer (ABACUS-2). Ann Oncol. 2023; 34: S1201–S1202.
  21. Vilaseca A, Jayram G, Raventos C, et al. LBA104 First safety and efficacy results of the TAR-210 erdafitinib (erda) intravesical delivery system in patients (pts) with non–muscle-invasive bladder cancer (NMIBC) with select FGFR alterations (alt). Ann Oncol. 2023; 34: S1343.
  22. Necchi A, Jacob JM, Daneshmand S, et al. LBA105 Results from SunRISe-1 in patients (Pts) with bacillus Calmette–Guérin (BCG)-unresponsive high-risk non–muscle-invasive bladder cancer (HR NMIBC) receiving TAR-200 monotherapy. Ann Oncol. 2023; 34: S1343–S1344.
  23. Sartor O, de Bono J, Chi KN, et al. VISION Investigators. Lutetium-177-PSMA-617 for Metastatic Castration-Resistant Prostate Cancer. N Engl J Med. 2021; 385(12): 1091–1103.
  24. Wysocki PJ, Chłosta P, Antoniewicz A, et al. Zalecenia postępowania diagnostyczno-terapeutycznego w raku gruczołu krokowego — stanowisko Polskiego Towarzystwa Onkologii Klinicznej i Polskiego Towarzystwa Urologicznego. Onkol Prakt Klin Edu. 2024; 10(1): 1–72.
  25. de Wit R, de Bono J, Sternberg CN, et al. CARD Investigators. Cabazitaxel versus Abiraterone or Enzalutamide in Metastatic Prostate Cancer. N Engl J Med. 2019; 381(26): 2506–2518.
  26. Sommer U, Siciliano T, Ebersbach C, et al. Impact of Androgen Receptor Activity on Prostate-Specific Membrane Antigen Expression in Prostate Cancer Cells. Int J Mol Sci. 2022; 23(3).
  27. Abida W, Cheng ML, Armenia J, et al. Analysis of the Prevalence of Microsatellite Instability in Prostate Cancer and Response to Immune Checkpoint Blockade. JAMA Oncol. 2019; 5(4): 471–478.
  28. Parker CC, Clarke NW, Cook AD, et al. Timing of radiotherapy after radical prostatectomy (RADICALS-RT): a randomised, controlled phase 3 trial. Lancet. 2020; 396(10260): 1413–1421.
  29. Wysocki PJ, Chłosta P, Chrzan R, et al. Zalecenia postępowania diagnostyczno-terapeutycznego w raku nerkowokomórkowym — aktualizacja. Onkol Prakt Klin Edu. 2022; 8(6): 424–457.
  30. Baldewijns MM, van Vlodrop IJH, Vermeulen PB, et al. VHL and HIF signalling in renal cell carcinogenesis. J Pathol. 2010; 221(2): 125–138.
  31. Wysocki PJ, Chłosta P, Chrzan R, et al. Zalecenia postępowania diagnostyczno-terapeutycznego w raku nerkowokomórkowym — aktualizacja. Onkologia w Praktyce Klinicznej - Edukacja. 2022;8(6):424-457. Link to the article PMID: Not applicable for non-journal articles To samo co 29??
  32. Choueiri TK, Bauer TM, Papadopoulos KP, et al. Inhibition of hypoxia-inducible factor-2α in renal cell carcinoma with belzutifan: a phase 1 trial and biomarker analysis. Nat Med. 2021; 27(5): 802–805.
  33. Albiges L, Rini BI, Peltola K, et al. LBA88 Belzutifan versus everolimus in participants (pts) with previously treated advanced clear cell renal cell carcinoma (ccRCC): Randomized open-label phase III LITESPARK-005 study. Ann Oncol. 2023; 34: S1329–S1330.
  34. Voss MH, Garmezy B, Kim SH, et al. 1883MO MEDI5752 (volrustomig), a novel PD-1/CTLA-4 bispecific antibody, in the first-line (1L) treatment of 65 patients (pts) with advanced clear cell renal cell carcinoma (aRCC). Ann Oncol. 2023; 34: S1012.
  35. Choueiri TK, Tomczak P, Park SeH, et al. KEYNOTE-564 Investigators. Adjuvant Pembrolizumab after Nephrectomy in Renal-Cell Carcinoma. N Engl J Med. 2021; 385(8): 683–694.
  36. Ryan CW, Tangen CM, Heath EI, et al. Adjuvant everolimus after surgery for renal cell carcinoma (EVEREST): a double-blind, placebo-controlled, randomised, phase 3 trial. Lancet. 2023; 402(10407): 1043–1051.
  37. Choueiri TK, Hessel C, Halabi S, et al. Cabozantinib versus sunitinib as initial therapy for metastatic renal cell carcinoma of intermediate or poor risk (Alliance A031203 CABOSUN randomised trial): Progression-free survival by independent review and overall survival update. Eur J Cancer. 2018; 94: 115–125.
  38. Choueiri TK, Escudier B, Powles T, et al. METEOR investigators. Cabozantinib versus everolimus in advanced renal cell carcinoma (METEOR): final results from a randomised, open-label, phase 3 trial. Lancet Oncol. 2016; 17(7): 917–927.
  39. Motzer R, Alekseev B, Rha SY, et al. CLEAR Trial Investigators. Lenvatinib plus Pembrolizumab or Everolimus for Advanced Renal Cell Carcinoma. N Engl J Med. 2021; 384(14): 1289–1300.
  40. Gruenwald V, McKay RR, Buchler T, et al. 1903P Tumor response by baseline metastases in patients (pts) with renal cell carcinoma (RCC) treated with lenvatinib (L) plus pembrolizumab (P) vs sunitinib (S): Post hoc analysis of the CLEAR trial. Ann Oncol. 2023; 34: S1024–S1025.
  41. Iacovelli R, Ciccarese C, Bersanelli M, et al. 1884MO Phase II study of avelumab (Ave) plus intermittent axitinib (Axi) in previously untreated patients (pts) with metastatic renal cell carcinoma (mRCC): The TIDE-A study. Ann Oncol. 2023; 34: S1013.