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Open Access 01-12-2023 | Urothelial Cancer | Editorial

Genitourinary cancers updates: highlights from ASCO 2023

Authors: Qian Qin, Hollie Sheffield, Sean M. Taasan, Andrew Z. Wang, Tian Zhang

Published in: Journal of Hematology & Oncology | Issue 1/2023

Abstract

Significant scientific advances in immunotherapy and targeted therapy approaches have improved clinical outcomes and increased treatment options for patients with genitourinary (GU) malignancies. We highlight the clinical trial developments released at the ASCO 2023 annual meeting, including PARP inhibitors for prostate cancer, antibody drug conjugates and fibroblast growth factor receptor inhibitors for urothelial cancer, and HIF2a inhibitors for renal cell carcinoma. Novel agents such as bispecific antibodies, chimeric antigen receptor T-cells, and radiopharmaceuticals are currently in early phase development and also have high potential impact for the GU cancer landscape. With more treatment options, the field will need to define best treatment sequencing to optimize outcomes for each patient.

Fizazi K, Foulon S, Carles J, Roubaud G, McDermott R, Fléchon A, et al. Abiraterone plus prednisone added to androgen deprivation therapy and docetaxel in de novo metastatic castration-sensitive prostate cancer (PEACE-1): a multicentre, open-label, randomised, phase 3 study with a 2 × 2 factorial design. Lancet. 2022;399(10336):1695–707.CrossRefPubMed

Agarwal N, Azad AA, Carles J, Fay AP, Matsubara N, Heinrich D, et al. Talazoparib plus enzalutamide in men with first-line metastatic castration-resistant prostate cancer (TALAPRO-2): a randomised, placebo-controlled, phase 3 trial. Lancet. 2023;402(10398):291–303.CrossRefPubMed

Tagawa ST, Sartor AO, Saad F, Reid AH, Sakharova OV, Feng FY, et al. PSMAddition: a phase 3 trial to compare treatment with 177Lu-PSMA-617 plus standard of care (SoC) and SoC alone in patients with metastatic hormone-sensitive prostate cancer. J Clin Oncol. 2023;41(16_suppl):TPS5116.CrossRef

Aggarwal RR, Zhang J, Monk P, Zhu X, Costin D, Petrylak DP, et al. First-in-class oral innate immune activator BXCL701 combined with pembrolizumab, in patients with metastatic castration-resistant prostate cancer (mCRPC) of small cell neuroendocrine (SCNC) variant: Randomized phase 2b trial. J Clin Oncol. 2023;41(16_suppl):TPS5109.CrossRef

Hawley JE, Dallos M, Lim EA, Runcie K, Hu J, Lowy I, et al. The PRIME-CUT study: a single-arm phase 2 study of ADT with PD-1 blockade and docetaxel in men with metastatic hormone-sensitive prostate cancer. J Clin Oncol. 2023;41(16_suppl):e17089.CrossRef

McKay RR, Armstrong AJ, Emamekhoo H, Gourdin TS, Heath EI, Hussain A, et al. The Maverick trial: a phase 2 study of abivertinib in patients (pts) with metastatic castration resistant prostate cancer (mCRPC). J Clin Oncol. 2023;41(16_suppl):TPS5106.CrossRef

Autio KA, Kyriakopoulos C, Xiao H, Emamekhoo H, Danila DC, Devitt ME, et al. A phase Ib/II study of intermittent talazoparib plus temozolomide in patients with metastatic castration-resistant prostate cancer (mCRPC) and no mutations in DNA damage repair (DDR). J Clin Oncol. 2023;41(16_suppl):e17036.CrossRef

Jani C, Xie W, Ajmera A, Araneta A, Jamieson C, Folefac E, et al. A phase 1/2 study of combination olaparib and radium-223 in men with metastatic castration-resistant prostate cancer with bone metastases (COMRADE): a trial in progress. J Clin Oncol. 2023;41(16_suppl):TPS5110.CrossRef

Vis A, Ettema R, Hendrikse H, van der Gaag S, Oprea-Lager DE. A feasibility study of 177Lu-PSMA radioligand therapy alternated with radium-223 in patients with bone-metastatic, oligo-metastatic, hormone-sensitive prostate cancer after curative therapy: the DUET study. J Clin Oncol. 2023;41(16_suppl):TPS5113.CrossRef

10.

Guo C, Crabb SJ, Pacey S, Coyle V, Danson S, Villacampa G, et al. A phase (Ph) I/II trial of abiraterone acetate in combination with tildrakizumab (anti-IL23 monoclonal antibody) in patients with metastatic castration-resistant prostate cancer (mCRPC). J Clin Oncol. 2023;41(16_suppl):TPS5105.CrossRef

11.

Zaretsky JM, Bansal D, Saeed MA, Peng B, Luo J, Klette J, et al. CABIOS trial: A phase Ib study of cabozantinib and nivolumab in combination with abiraterone in patients (pts) with metastatic hormone sensitive prostate cancer (mHSPC). J Clin Oncol. 2023;41(16_suppl):5084.CrossRef

12.

Sandhu S, Joshua AM, Emmett L, Crumbaker M, Bressel M, Huynh R, et al. LuPARP: Phase 1 trial of 177Lu-PSMA-617 and olaparib in patients with metastatic castration resistant prostate cancer (mCRPC). J Clin Oncol. 2023;41(16_suppl):5005.CrossRef

13.

Hackenbruch C, Heitmann JS, Walz JS, Federmann B, Pflügler M, Hadaschik BA, et al. ProSperA: Phase I study to evaluate safety, tolerability and preliminary efficacy of a bispecific PSMAxCD3 antibody in men with biochemical recurrence of prostate cancer. J Clin Oncol. 2023;41(16_suppl):TPS5114.CrossRef

14.

Dorff TB, Blanchard S, Martirosyan H, Adkins L, Dhapola G, Shishido S, et al. Final results from phase I study of PSCA-targeted chimeric antigen receptor (CAR) T cells in patients with metastatic castration resistant prostate cancer (mCRPC). J Clin Oncol. 2023;41(16_suppl):5019.CrossRef

15.

Bossi A, Foulon S, Maldonado X, Sargos P, McDermott RS, Flechon A, et al. Prostate irradiation in men with de novo, low-volume, metastatic, castration-sensitive prostate cancer (mCSPC): results of PEACE-1, a phase 3 randomized trial with a 2x2 design. J Clin Oncol. 2023;41(17_suppl):LBA5000.CrossRef

16.

Fizazi K, Azad A, Matsubara N, Carles J, Fay AP, De Giorgi U, et al. TALAPRO-2: Phase 3 study of talazoparib (TALA) + enzalutamide (ENZA) versus placebo (PBO) + ENZA as first-line (1L) treatment for patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) harboring homologous recombination repair (HRR) gene alterations. J Clin Oncol. 2023;41(16_suppl):5004.CrossRef

17.

Gupta S, Rosenberg JE, McKay RR, Flaig TW, Petrylak DP, Hoimes CJ, et al. Study EV-103 dose escalation/cohort A: long-term outcome of enfortumab vedotin + pembrolizumab in first-line (1L) cisplatin-ineligible locally advanced or metastatic urothelial carcinoma (la/mUC) with nearly 4 years of follow-up. J Clin Oncol. 2023;41(16_suppl):4505.CrossRef

18.

Loriot Y, Matsubara N, Park SH, Huddart RA, Burgess EF, Houede N, et al. Phase 3 THOR study: Results of erdafitinib (erda) versus chemotherapy (chemo) in patients (pts) with advanced or metastatic urothelial cancer (mUC) with select fibroblast growth factor receptor alterations (FGFRalt). J Clin Oncol. 2023;41(17_suppl):LBA4619.CrossRef

19.

Siefker-Radtke AO, Powles T, Moreno V, Kang TW, Cicin I, Girvin A, et al. Erdafitinib (ERDA) vs ERDA plus cetrelimab (ERDA+CET) for patients (pts) with metastatic urothelial carcinoma (mUC) and fibroblast growth factor receptor alterations (FGFRa): final results from the phase 2 Norse study. J Clin Oncol. 2023;41(16_suppl):4504.CrossRef

20.

Powles T, Rosenberg JE, Sonpavde GP, Loriot Y, Durán I, Lee JL, et al. Enfortumab vedotin in previously treated advanced urothelial Carcinoma. N Engl J Med. 2021;384(12):1125–35.CrossRefPubMedPubMedCentral

21.

Powles T P-VB, Gupta S, Bedke J, Kikuchi E, Hoffman-Censits J, Iyer G, Vulsteke C, Park SH, Shin SJ, Sauna D, Fornarini G, Li J-R, Gumus M, Mar N, Narayanan S, Yu X, Gorla S, Moreno B, Van der Heijden M, editor EV-302/Keynote-A39: open-label, randomized phase III study of enfortumab Bedouin in combination with pembrolizumab (EV+P) vs chemotherapy (Chemo) in previously untreated locally advanced metastatic urothelial carcinoma (la/mUC). ESMO Congress; 2023 October 10, 2023; Madrid.

22.

Tagawa ST, Balar AV, Petrylak DP, Rezazadeh A, Loriot Y, Flechon A, et al. Updated outcomes in TROPHY-U-01 cohort 1, a phase 2 study of sacituzumab govitecan (SG) in patients (pts) with metastatic urothelial cancer (mUC) that progressed after platinum (PT)-based chemotherapy and a checkpoint inhibitor (CPI). J Clin Oncol. 2023;41(6_suppl):526.CrossRef

23.

Pal SK, Albiges L, Tomczak P, Suárez C, Voss MH, de Velasco G, et al. Atezolizumab plus cabozantinib versus cabozantinib monotherapy for patients with renal cell carcinoma after progression with previous immune checkpoint inhibitor treatment (CONTACT-03): a multicentre, randomised, open-label, phase 3 trial. Lancet. 2023;402(10397):185–95.CrossRefPubMed

24.

Choueiri TK, Albiges L, Tomczak P, Suárez C, Voss MH, de Velasco G, et al. Efficacy and safety of atezolizumab plus cabozantinib vs cabozantinib alone after progression with prior immune checkpoint inhibitor (ICI) treatment in metastatic renal cell carcinoma (RCC): primary PFS analysis from the phase 3, randomized, open-label CONTACT-03 study. J Clin Oncol. 2023;41(17):4500.CrossRef

25.

Albiges L, Beckermann K, Miller WH, Goh JC, Gajate P, Harris CA, et al. Belzutifan plus lenvatinib for patients (pts) with advanced clear cell renal cell carcinoma (ccRCC) after progression on a PD-1/L1 and VEGF inhibitor: preliminary results of arm B5 of the phase 1/2 KEYMAKER-U03B study. J Clin Oncol. 2023;41(16_suppl):4553.CrossRef

26.

Beckermann K, Campbell MT, Haas NB, Ornstein MC, Gao X, Mao SS, et al. Phase 2 study of batiraxcept (AVB-S6–500, an AXL inhibitor) as monotherapy, in combination with cabozantinib (cabo), and in combination with cabo and nivolumab (nivo) in patients with advanced clear cell renal cell carcinoma (ccRCC). J Clin Oncol. 2023;41(16_suppl):4534.CrossRef

27.

Pili R, Haas NB, Monk P, Logan TF, Narayan V, Burney H, Adra N. A phase I/II study to evaluate the safety, pharmacodynamics, and efficacy of entinostat in combination with atezolizumab and bevacizumab in patients with renal cell carcinoma. J Clin Oncol. 2023;41(16_suppl):4526.CrossRef

28.

Hasanov E, Flynt L, Slack Tidwell R, Hwang H, Brooks R, Wood LM, et al. Phase 1b/2 study of combination 177Lu girentuximab plus cabozantinib and nivolumab in treatment naïve patients with advanced clear cell RCC. J Clin Oncol. 2023;41(16_suppl):4605.CrossRef

29.

McDermott DF, Peer A, Agarwal N, Atkins MB, Cornell J, Perini RF, et al. LITESPARK-024: a randomized phase 1/2 study of belzutifan with or without palbociclib in patients with advanced renal cell carcinoma. J Clin Oncol. 2023;41(6_suppl):747.CrossRef

30.

Lee C-H, Voss MH, Carlo MI, Chen Y-B, Zucker M, Knezevic A, et al. Phase II trial of cabozantinib plus nivolumab in patients with non–clear-cell renal cell carcinoma and genomic correlates. J Clin Oncol. 2022;40(21):2333–41.CrossRefPubMedPubMedCentral

31.

Pal SK, McGregor B, Suárez C, Tsao C-K, Kelly W, Vaishampayan U, et al. Cabozantinib in combination with atezolizumab for advanced renal cell carcinoma: results from the COSMIC-021 study. J Clin Oncol. 2021;39(33):3725–36.CrossRefPubMedPubMedCentral

32.

Lee C-H, Gurney H, Atduev V, Suárez C, Climent Duran MA, Pook DW, et al. First-line lenvatinib + pembrolizumab treatment across non-clear cell renal cell carcinomas: Results of the phase 2 KEYNOTE-B61 study. J Clin Oncol. 2023;41(16_suppl):4518.CrossRef

33.

Albiges L, Gurney H, Atduev V, Suarez C, Climent MA, Pook D, et al. Pembrolizumab plus lenvatinib as first-line therapy for advanced non-clear-cell renal cell carcinoma (KEYNOTE-B61): a single-arm, multicentre, phase 2 trial. Lancet Oncol. 2023;24(8):881–91.CrossRefPubMed

34.

Motzer R, Alekseev B, Rha SY, Porta C, Eto M, Powles T, et al. Lenvatinib plus pembrolizumab or everolimus for advanced renal cell Carcinoma. N Engl J Med. 2021;384(14):1289–300.CrossRefPubMed

35.

McGregor BA, Huang J, Xie W, Xu W, Bilen MA, Braun DA, et al. Phase II study of cabozantinib (Cabo) with nivolumab (Nivo) and ipilimumab (Ipi) in advanced renal cell carcinoma with variant histologies (RCCvh). J Clin Oncol. 2023;41(16_suppl):4520.CrossRef

36.

Choueiri TK, Powles T, Albiges L, Burotto M, Szczylik C, Zurawski B, et al. Cabozantinib plus Nivolumab and Ipilimumab in Renal-Cell Carcinoma. N Engl J Med. 2023;388(19):1767–78.CrossRefPubMedPubMedCentral

Title: Genitourinary cancers updates: highlights from ASCO 2023
Authors: Qian Qin
Hollie Sheffield
Sean M. Taasan
Andrew Z. Wang
Tian Zhang
Publication date: 01-12-2023
Publisher: BioMed Central
Keywords: Urothelial Cancer
Urothelial Cancer
Cabozantinib
Prostate Cancer
Prostate Cancer
Published in: Journal of Hematology & Oncology / Issue 1/2023
Electronic ISSN: 1756-8722
DOI: https://doi.org/10.1186/s13045-023-01511-8

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