258
Views
0
CrossRef citations to date
0
Altmetric
Perspective

Perspectives on the future of urothelial carcinoma therapy: chemotherapy and beyond

, , , , , , ORCID Icon, ORCID Icon, , , , ORCID Icon, , , & ORCID Icon show all
Pages 177-195 | Received 08 Aug 2022, Accepted 19 Nov 2022, Published online: 29 Nov 2022

References

  • Sakr SA, Mahran HA, Fahmy AM, et al. Expression of c-erb-B2 gene in bladder cancer of Egyptian patients and its correlation with p53 and bcl-2. Biomed Pharmacother. 2015 Dec;76:73–81. Epub 2015 Nov 10. PMID: 26653553 doi: 10.1016/j.biopha.2015.10.021
  • Richters A, Aben KKH, Lalm K. The global burden of urinary bladder cancer: an update. World J Urol. 2020Aug;38(8):1895–1904. Epub 2019 Nov 1. PMID: 31676912; PMCID: PMC7363726.
  • National Cancer Institute. 2022 SEER Cancer Stat Facts [cited 2022 Jul 13]. Avaiable from: https://seer.cancer.gov/statfacts/html/urinb.html
  • Babjuk M, Burger M, Compérat EM, et al. European association of urology guidelines on non-muscle-invasive bladder cancer (TaT1 and carcinoma in situ) - 2019 update. Eur Urol. 2019Nov;76(5):639–657. Epub 2019 Aug 20. PMID: 31443960
  • Aragon-Ching JB, Werntz RP, Zietman AL, et al. Multidisciplinary management of muscle-invasive bladder cancer: current challenges and future directions. Am Soc Clin Oncol Educ Book. 2018May23;38(38):307–318.
  • Bellmunt J, Orsola A, Leow JJ, et al. Bladder cancer: ESMO Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2014Sep;25(3):iii40–8. Epub 2014 Aug 5. PMID: 25096609
  • Milowsky MI, Rumble RB, Booth CM, et al. Guideline on muscle-invasive and metastatic bladder cancer (European association of urology guideline): American society of clinical oncology clinical practice guideline endorsement. J Clin Oncol. 2016Jun1;34(16):1945–1952.
  • Houssiau H, Seront E. Improving the role of immune checkpoint inhibitors in the management of advanced urothelial carcinoma, where do we stand? Transl Oncol. 2022May; 19: 101387. Epub 2022 Mar 9. PMID: 35278793; PMCID: PMC8917314. doi:10.1016/j.tranon.2022.101387.
  • von der Maase H, Hansen SW, Roberts JT, et al. Gemcitabine and cisplatin versus methotrexate, vinblastine, doxorubicin, and cisplatin in advanced or metastatic bladder cancer: results of a large, randomized, multinational, multicenter, phase III study. J Clin Oncol. 2000Sep;18(17):3068–3077. PMID: 11001674
  • Sternberg CN, Yagoda A, Scher HI, et al. Methotrexate, vinblastine, doxorubicin, and cisplatin for advanced transitional cell carcinoma of the urothelium. Efficacy and patterns of response and relapse. Cancer. 1989Dec15;64(12):2448–2458.
  • Bamias A, Tzannis K, Harshman LC, et al. Impact of contemporary patterns of chemotherapy utilization on survival in patients with advanced cancer of the urinary tract: a Retrospective International Study of Invasive/Advanced Cancer of the Urothelium (RISC). Ann Oncol. 2019Nov1;30(11):1841.
  • Reesink DJ, van de Garde EMW, Peters BJM, et al. Treatment patterns and clinical outcomes of chemotherapy treatment in patients with muscle-invasive or metastatic bladder cancer in the Netherlands. Sci Rep. 2020Sep25;10(1):15822.
  • Apolo AB, Infante JR, Balmanoukian A, et al. Avelumab, an anti-programmed death-ligand 1 antibody, in patients with refractory metastatic urothelial carcinoma: results from a multicenter, phase ib study. J Clin Oncol. 2017Jul1;35(19):2117–2124.
  • Sharma P, Retz M, Siefker-Radtke A, et al. Nivolumab in metastatic urothelial carcinoma after platinum therapy (CheckMate 275): a multicentre, single-arm, phase 2 trial. Lancet Oncol. 2017Mar;18(3):312–322. Epub 2017 Jan 26. PMID: 28131785
  • Bellmunt J, de Wit R, Vaughn DJ, et al. Pembrolizumab as second-line therapy for advanced urothelial carcinoma. N Engl J Med. 2017Mar16;376(11):1015–1026.
  • Rosenberg JE, Hoffman-Censits J, Powles T, et al. Atezolizumab in patients with locally advanced and metastatic urothelial carcinoma who have progressed following treatment with platinum-based chemotherapy: a single-arm, multicentre, phase 2 trial. Lancet. 2016May7;387(10031):1909–1920.
  • Balar AV, Galsky MD, Rosenberg JE, et al. Atezolizumab as first-line treatment in cisplatin-ineligible patients with locally advanced and metastatic urothelial carcinoma: a single-arm, multicentre, phase 2 trial. Lancet. 2017Jan7;389(10064):67–76.
  • Patel MR, Ellerton J, Infante JR, et al. Avelumab in metastatic urothelial carcinoma after platinum failure (JAVELIN Solid Tumor): pooled results from two expansion cohorts of an open-label, phase 1 trial. Lancet Oncol. 2018Jan;19(1):51–64. Epub 2017 Dec 5. Erratum in: Lancet Oncol. 2018 Jul;19(7):e335. PMID: 29217288; PMCID: PMC7984727
  • Powles T, O’Donnell PH, Massard C, et al. Efficacy and safety of durvalumab in locally advanced or metastatic urothelial carcinoma: updated results from a phase 1/2 open-label Study. JAMA Oncol. 2017Sep14;3(9):e172411.
  • Okan Cakir M, Kirca O, Gunduz S, et al. Hyperprogression after immunotherapy: a comprehensive review. J BUON. 2019Nov-Dec; 24(6):2232–2241. PMID: 31983088
  • Sternberg CN, Yagoda A, Scher HI, et al. Preliminary results of M-VAC (methotrexate, vinblastine, doxorubicin and cisplatin) for transitional cell carcinoma of the urothelium. J Urol. 1985Mar;133(3):403–407. PMID: 4038749
  • Wu T, Wu Y, Chen S, et al. Curative effect and survival assessment comparing gemcitabine and cisplatin versus methotrexate, vinblastine, doxorubicin and cisplatin as neoadjuvant therapy for bladder cancer: a systematic review and meta-analysis. Front Oncol. 2021 Nov 25;11:678896. PMID: 34900663; PMCID: PMC8656312. DOI:10.3389/fonc.2021.678896
  • Gakis G, Morgan TM, Daneshmand S, et al. Impact of perioperative chemotherapy on survival in patients with advanced primary urethral cancer: results of the international collaboration on primary urethral carcinoma. Ann Oncol. 2015Aug;26(8):1754–1759. Epub 2015 May 12. PMID: 25969370
  • Meng X, Chao B, Vijay V, et al. High response rates to neoadjuvant chemotherapy in high-grade upper tract urothelial carcinoma. Urology. 2019 Jul;129:146–152. Epub 2019 Mar 28. PMID: 30930207 doi:10.1016/j.urology.2019.01.058
  • Svatek RS, Shariat SF, Novara G, et al. Discrepancy between clinical and pathological stage: external validation of the impact on prognosis in an international radical cystectomy cohort. BJU Int. 2011Mar;107(6):898–904. Epub 2011 Jan 18. PMID: 21244604
  • Margulis V, Shariat SF, Ashfaq R, et al. Ki-67 is an independent predictor of bladder cancer outcome in patients treated with radical cystectomy for organ-confined disease. Clin Cancer Res. 2006Dec15;12(24):7369–7373.
  • Karakiewicz PI, Shariat SF, Palapattu GS, et al. Precystectomy nomogram for prediction of advanced bladder cancer stage. Eur Urol. 2006 Dec;50(6):1254–1260. discussion 1261-2. Epub 2006 Jun 23. PMID: 16831511.
  • Xylinas E, Rink M, Margulis V, et al. Impact of renal function on eligibility for chemotherapy and survival in patients who have undergone radical nephro-ureterectomy. BJU Int. 2013Aug;112(4):453–461. Epub 2013 Mar 6. PMID: 23464979
  • Yin M, Joshi M, Meijer RP, et al. Neoadjuvant chemotherapy for muscle-invasive bladder cancer: a systematic review and two-step meta-analysis. Oncologist. 2016Jun;21(6):708–715. Epub 2016 Apr 6. PMID: 27053504; PMCID: PMC4912364
  • Leow JJ, Chong YL, Chang SL, et al. Neoadjuvant and adjuvant chemotherapy for upper tract urothelial carcinoma: a 2020 systematic review and meta-analysis, and future perspectives on systemic therapy. Eur Urol. 2021May;79(5):635–654. Epub 2020 Aug 12. PMID: 32798146
  • Foerster B, Abufaraj M, Petros F, et al. Efficacy of preoperative chemotherapy for high risk upper tract urothelial carcinoma. J Urol. 2020Jun;203(6):1101–1108. Epub 2020 Jan 2. PMID: 31898919
  • Grossman HB, Natale RB, Tangen CM, et al. Neoadjuvant chemotherapy plus cystectomy compared with cystectomy alone for locally advanced bladder cancer. N Engl J Med. 2003Aug28;349(9):859–866.
  • Sternberg CN, de Mulder P, Schornagel JH, et al. Seven year update of an EORTC phase III trial of high-dose intensity M-VAC chemotherapy and G-CSF versus classic M-VAC in advanced urothelial tract tumours. Eur J Cancer. 2006Jan;42(1):50–54. Epub 2005 Dec 5. PMID: 16330205
  • Plimack ER, Hoffman-Censits JH, Viterbo R, et al. Accelerated methotrexate, vinblastine, doxorubicin, and cisplatin is safe, effective, and efficient neoadjuvant treatment for muscle-invasive bladder cancer: results of a multicenter phase II study with molecular correlates of response and toxicity. J Clin Oncol. 2014Jun20;32(18):1895–1901.
  • Margulis V, Puligandla M, Trabulsi EJ, et al. Phase II trial of neoadjuvant systemic chemotherapy followed by extirpative surgery in patients with high grade upper tract urothelial carcinoma. J Urol. 2020Apr;203(4):690–698. Epub 2019 Nov 8. PMID: 31702432; PMCID: PMC7735436
  • Niedersüss-Beke D, Puntus T, Kunit T, et al. Neoadjuvant chemotherapy with gemcitabine plus cisplatin in patients with locally advanced bladder cancer. Oncology. 2017;93(1):36–42. Epub 2017 Apr 12. PMID: 28399521.
  • Hosogoe S, Hatakeyama S, Kusaka A, et al. Platinum-based neoadjuvant chemotherapy improves oncological outcomes in patients with locally advanced upper tract urothelial carcinoma. Eur Urol Focus. 2018Dec;4(6):946–953. Epub 2017 Apr 7. PMID: 28753881
  • Pfister C, Gravis G, Fléchon A, et al. Dose-dense methotrexate, vinblastine, doxorubicin, and cisplatin or gemcitabine and cisplatin as perioperative chemotherapy for patients with nonmetastatic muscle-invasive bladder cancer: results of the GETUG-AFU V05 VESPER trial. J Clin Oncol. 2022Mar7;40(18):2013–2022
  • Liu T, Jiang G. A systematic review and meta-analysis of neoadjuvant chemotherapy for bladder cancer between ddMVAC and GC regimen. Urol Oncol. 2022May;40(5):195.e19–195.e25. Epub 2021 Dec 20. PMID: 34949512.
  • Shariat SF, Chade DC, Karakiewicz PI, et al. Combination of multiple molecular markers can improve prognostication in patients with locally advanced and lymph node positive bladder cancer. J Urol. 2010Jan;183(1):68–75. PMID: 19913255
  • Xylinas E, Rink M, Robinson BD, et al. Impact of histological variants on oncological outcomes of patients with urothelial carcinoma of the bladder treated with radical cystectomy. Eur J Cancer. 2013May;49(8):1889–1897. Epub 2013 Mar 4. PMID: 23466126
  • Svatek RS, Shariat SF, Lasky RE, et al. The effectiveness of off-protocol adjuvant chemotherapy for patients with urothelial carcinoma of the urinary bladder. Clin Cancer Res. 2010Sep1;16(17):4461–4467.
  • Aziz A, May M, Burger M, et al. Prediction of 90-day mortality after radical cystectomy for bladder cancer in a prospective European multicenter cohort. Eur Urol. 2014Jul;66(1):156–163. Epub 2013 Dec 27. PMID: 24388438
  • Dayyani F, Pettaway CA, Kamat AM, et al. Retrospective analysis of survival outcomes and the role of cisplatin-based chemotherapy in patients with urethral carcinomas referred to medical oncologists. Urol Oncol. 2013Oct;31(7):1171–1177. Epub 2012 Apr 24. PMID: 22534087; PMCID: PMC4131852
  • Hird AE, Magee DE, Cheung DC, et al. Neoadjuvant versus adjuvant chemotherapy for upper tract urothelial carcinoma: a microsimulation model. Clin Genitourin Cancer. 2021Apr;19(2):e135–e147. Epub 2020 Oct 13. PMID: 33168398
  • Sternberg CN, Skoneczna I, Kerst JM, et al. Immediate versus deferred chemotherapy after radical cystectomy in patients with pT3-pT4 or N+ M0 urothelial carcinoma of the bladder (EORTC 30994): an intergroup, open-label, randomised phase 3 trial. Lancet Oncol. 2015Jan;16(1):76–86. Epub 2014 Dec 11. PMID: 25498218
  • Birtle A, Johnson M, Chester J, et al. Adjuvant chemotherapy in upper tract urothelial carcinoma (the POUT trial): a phase 3, open-label, randomised controlled trial. Lancet. 2020Apr18;395(10232):1268–1277.
  • Galsky MD, Stensland KD, Moshier E, et al. Effectiveness of adjuvant chemotherapy for locally advanced bladder cancer. J Clin Oncol. 2016Mar10;34(8):825–832.
  • Berg S, D’Andrea D, Vetterlein MW, et al. Impact of adjuvant chemotherapy in patients with adverse features and variant histology at radical cystectomy for muscle-invasive carcinoma of the bladder: does histologic subtype matter? Cancer. 2019May1;125(9):1449–1458.
  • Lucca I, Rouprêt M, Kluth L, et al. Adjuvant cisplatin-based combined chemotherapy for lymph node (LN)-positive urothelial carcinoma of the bladder (UCB) after radical cystectomy (RC): a retrospective international study of >1500 patients. BJU Int. 2015May;115(5):722–727. Epub 2015 Jan 26. PMID: 24905084
  • Laukhtina E, Sari Motlagh R, Mori K, et al. Chemotherapy is superior to checkpoint inhibitors after radical surgery for urothelial carcinoma: a systematic review and network meta-analysis of oncologic and toxicity outcomes. Crit Rev Oncol Hematol. 2022 Jan;169:103570. Epub 2021 Dec 10. PMID: 34902554 doi:10.1016/j.critrevonc.2021.103570
  • von der Maase H, Sengelov L, Roberts JT, et al. Long-term survival results of a randomized trial comparing gemcitabine plus cisplatin, with methotrexate, vinblastine, doxorubicin, plus cisplatin in patients with bladder cancer. J Clin Oncol. 2005Jul20;23(21):4602–4608.
  • De Santis M, Bellmunt J, Mead G, et al. Randomized phase II/III trial assessing gemcitabine/carboplatin and methotrexate/carboplatin/vinblastine in patients with advanced urothelial cancer who are unfit for cisplatin-based chemotherapy: EORTC study 30986. J Clin Oncol. 2012Jan10;30(2):191–199.
  • Galsky MD, Chen GJ, Oh WK, et al. Comparative effectiveness of cisplatin-based and carboplatin-based chemotherapy for treatment of advanced urothelial carcinoma. Ann Oncol. 2012Feb;23(2):406–410. Epub 2011 May 4. PMID: 21543626
  • Mori K, Schuettfort VM, Yanagisawa T, et al. Reassessment of the efficacy of carboplatin for metastatic urothelial carcinoma in the era of immunotherapy: a systematic review and meta-analysis. Eur Urol Focus. 2022 Mar 9;S2405-4569(22):00052–9. Epub ahead of print. PMID: 35279408.
  • Martini A, Raggi D, Fallara G, et al. Immunotherapy versus chemotherapy as first-line treatment for advanced urothelial cancer: a systematic review and meta-analysis. Cancer Treat Rev. 2022 Mar;104:102360. Epub 2022 Feb 10. PMID: 35176685 doi:10.1016/j.ctrv.2022.102360
  • Mori K, Pradere B, Moschini M, et al. First-line immune-checkpoint inhibitor combination therapy for chemotherapy-eligible patients with metastatic urothelial carcinoma: a systematic review and meta-analysis. Eur J Cancer. 2021 Jul;151:35–48. Epub 2021 May 4. PMID: 33962359 doi:10.1016/j.ejca.2021.03.049
  • Li H, Ni M, Xue C, et al. Optimal first-line treatment for platinum-eligible metastatic urothelial carcinoma: comparison of chemo-immunotherapy, immunotherapy, and chemotherapy- A systematic review and meta-analysis. Clin Immunol. 2022 Mar;236:108927. Epub 2022 Jan 11. PMID: 35031491 doi:10.1016/j.clim.2022.108927
  • Powles T, Csőszi T, Özgüroğlu M, et al. 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. 2021Jul;22(7):931–945. Epub 2021 May 26. PMID: 34051178
  • Galsky MD, Arija JÁA, Bamias A, et al. Atezolizumab with or without chemotherapy in metastatic urothelial cancer (IMvigor130): a multicentre, randomised, placebo-controlled phase 3 trial. Lancet. 2020May16;395(10236):1547–1557.
  • Powles T, van der Heijden MS, Castellano D, et al. Durvalumab alone and durvalumab plus tremelimumab versus chemotherapy in previously untreated patients with unresectable, locally advanced or metastatic urothelial carcinoma (Danube): a randomised, open-label, multicentre, phase 3 trial. Lancet Oncol. 2020 Dec;21(12):1574–1588.
  • Powles T, Park SH, Voog E, et al. Avelumab maintenance therapy for advanced or metastatic urothelial carcinoma. N Engl J Med. 2020Sep24;383(13):1218–1230.
  • Balar AV, Castellano D, O’Donnell PH, et al. First-line pembrolizumab in cisplatin-ineligible patients with locally advanced and unresectable or metastatic urothelial cancer (KEYNOTE-052): a multicentre, single-arm, phase 2 study. Lancet Oncol. 2017Nov;18(11):1483–1492. Epub 2017 Sep 26. PMID: 28967485
  • Wong RL, Ferris LA, Do OA, et al. Efficacy of platinum rechallenge in metastatic urothelial carcinoma after previous platinum-based chemotherapy for metastatic disease. Oncologist. 2021Dec;26(12):1026–1034. Epub 2021 Aug 17. PMID: 34355457; PMCID: PMC8649023
  • Sternberg CN, Calabrò F, Pizzocaro G, et al. Chemotherapy with an every-2-week regimen of gemcitabine and paclitaxel in patients with transitional cell carcinoma who have received prior cisplatin-based therapy. Cancer. 2001Dec15;92(12):2993–2998.
  • Raggi D, Miceli R, Sonpavde G, et al. Second-line single-agent versus doublet chemotherapy as salvage therapy for metastatic urothelial cancer: a systematic review and meta-analysis. Ann Oncol. 2016Jan;27(1):49–61. Epub 2015 Oct 20. PMID: 26487582
  • Albers P, Park SI, Niegisch G, et al. Randomized phase III trial of 2nd line gemcitabine and paclitaxel chemotherapy in patients with advanced bladder cancer: short-term versus prolonged treatment [German Association of Urological Oncology (AUO) trial AB 20/99]. Ann Oncol. 2011Feb;22(2):288–294. Epub 2010 Aug 2. PMID: 20682548
  • Bellmunt J, Théodore C, Demkov T, et al. Phase III trial of vinflunine plus best supportive care compared with best supportive care alone after a platinum-containing regimen in patients with advanced transitional cell carcinoma of the urothelial tract. J Clin Oncol. 2009 Sep 20;27(27):4454–4461.
  • Quinn DI, Ruel N, Twardowski P, et al. Newman. Eribulin in advanced urothelial cancer (AUC) patients (pts): a California Cancer Consortium trial—NCI/CTEP 7435. J clin oncol. 2015;33(15_suppl):4504–4504.
  • Sadeghi S, Groshen SG, Tsao-Wei DD, et al. Phase II California cancer consortium trial of gemcitabine-eribulin combination in cisplatin-ineligible patients with metastatic urothelial carcinoma: final report (NCI-9653). J Clin Oncol. 2019Oct10;37(29):2682–2688.
  • Gotwals P, Cameron S, Cipolletta D, et al. Prospects for combining targeted and conventional cancer therapy with immunotherapy. Nat Rev Cancer. 2017May;17(5):286–301. Epub 2017 Mar 24. PMID: 28338065
  • Galluzzi L, Buqué A, Kepp O, et al. Immunological effects of conventional chemotherapy and targeted anticancer agents. Cancer Cell. 2015Dec14;28(6):690–714.
  • Powles T, Kockx M, Rodriguez-Vida A, et al. Clinical efficacy and biomarker analysis of neoadjuvant atezolizumab in operable urothelial carcinoma in the ABACUS trial. Nat Med. 2019 Nov;25(11):1706–1714.
  • Necchi A, Anichini A, Raggi D, et al. Pembrolizumab as neoadjuvant therapy before radical cystectomy in patients with muscle-invasive urothelial bladder carcinoma (PURE-01): an open-label, single-arm, phase II study. J Clin Oncol. 2018Dec1;36(34):3353–3360.
  • Gupta S, Sonpavde G, Weight CJ, et al. Results from BLASST-1 (Bladder cancer signal seeking trial) of nivolumab, gemcitabine, and cisplatin in muscle invasive bladder cancer (MIBC) undergoing cystectomy. J clin oncol. 2020;38(6_suppl):439–439.
  • Rose TL, Harrison MR, Deal AM, et al. Phase II study of gemcitabine and split-dose cisplatin plus pembrolizumab as neoadjuvant therapy before radical cystectomy in patients with muscle-invasive bladder cancer. J Clin Oncol. 2021Oct1;39(28):3140–3148.
  • Funt SA, Lattanzi M, Whiting K, et al. Neoadjuvant atezolizumab with gemcitabine and cisplatin in patients with muscle-invasive bladder cancer: a multicenter, single-arm, phase II trial. J Clin Oncol. 2022Apr20;40(12):1312–1322.
  • Giannatempo P, Raggi D, Marandino L, et al. Pembrolizumab and nab-paclitaxel as salvage therapy for platinum-treated, locally advanced or metastatic urothelial carcinoma: interim results of the open-label, single-arm, phase II PEANUT study. Ann Oncol. 2020Dec;31(12):1764–1772. Epub 2020 Sep 23. PMID: 32979512
  • Garje R, Packiam VT, Koski A, et al. Phase Ib study of avelumab and taxane based chemotherapy in platinum-refractory or ineligible metastatic urothelial cancer (AVETAX study). J clin oncol. 2022 40; 40(6_suppl):503–503.
  • Sievers EL, Senter PD. Antibody-drug conjugates in cancer therapy. Annu Rev Med. 2013;64(1):15–29. Epub 2012 Oct 3. PMID: 23043493.
  • Sliwkowski MX, Mellman I. Antibody therapeutics in cancer. Science. 2013Sep13;341(6151):1192–1198. PMID: 24031011.
  • Powles T, Rosenberg JE, Sonpavde GP, et al. Enfortumab vedotin in previously treated advanced urothelial carcinoma. N Engl J Med. 2021Mar25;384(12):1125–1135. Epub 2021 Feb 12. PMID: 33577729; PMCID: PMC8450892.
  • Yu EY, Petrylak DP, O’Donnell PH, et al. Enfortumab vedotin after PD-1 or PD-L1 inhibitors in cisplatin-ineligible patients with advanced urothelial carcinoma (EV‑201): a multicentre, single-arm, phase 2 trial. Lancet Oncol. 2021 Jun;22(6):872–882.
  • Tagawa ST, Balar AV, Petrylak DP, et al. TROPHY-U-01: a phase II Open-label study of sacituzumab govitecan in patients with metastatic urothelial carcinoma progressing after platinum-based chemotherapy and checkpoint inhibitors. J Clin Oncol. 2021Aug1;39(22):2474–2485.
  • Sheng X, Yan X, Wang L, et al. Open-label, multicenter, phase II study of RC48-ADC, a HER2-targeting antibody-drug conjugate, in patients with locally advanced or metastatic urothelial carcinoma. Clin Cancer Res. 2021Jan1;27(1):43–51.
  • Xu H, Sheng X, Yan X, et al. A phase II study of RC48-ADC in HER2-negative patients with locally advanced or metastatic urothelial carcinoma. J clin oncol. 2020;38(15_suppl):e17113–e17113.
  • Qu W, Fu C, Han W, et al. MRG002-006: a multicenter phase II clinical trial of MRG002-ADC for unresectable locally advanced or metastatic urothelial cancer. J clin oncol. 2022;40(16_suppl):4570–4570.
  • de Bono JS, Concin N, Hong DS, et al. Tisotumab vedotin in patients with advanced or metastatic solid tumours (InnovaTV 201): a first-in-human, multicentre, phase 1-2 trial. Lancet Oncol. 2019Mar;20(3):383–393. Epub 2019 Feb 8. Erratum in: Lancet Oncol. 2019 Dec;20(12):e663. PMID: 30745090
  • Petrylak DP, Heath EI, Sonpavde G, et al. Anti-tumor activity, safety and pharmacokinetics (PK) of AGS15E (ASG-15ME) in a phase I dose escalation trial in patients (Pts) with metastatic urothelial cancer (mUC). J clin oncol. 2016;34(15_suppl):4532–4532.
  • Liu Y, Lian W, Zhao X, et al. A first in-human study of A166 in patients with locally advanced/metastatic solid tumors which are HER2-positive or HER2-amplified who did not respond or stopped responding to approved therapies. J clin oncol. 2020;38(15_suppl):1049–1049.
  • Nicolò E, Giugliano F, Ascione L, et al. Combining antibody-drug conjugates with immunotherapy in solid tumors: current landscape and future perspectives. Cancer Treat Rev. 2022 May;106:102395. Epub 2022 Apr 18. PMID: 35468539. doi:10.1016/j.ctrv.2022.102395
  • Friedlander TW, Milowsky MI, Asim Bilen M, et al. Study EV-103: update on durability results and long term outcome of enfortumab vedotin + pembrolizumab in first line locally advanced or metastatic urothelial carcinoma (la/mUC). J clin oncol. 2021;39(15_suppl):4528–4528.
  • Zhou L, Xu H, Li S, et al. Study RC48-C014: preliminary results of RC48-ADC combined with toripalimab in patients with locally advanced or metastatic urothelial carcinoma. J clin oncol. 2022 40; 6_suppl(6_suppl):515–515.
  • Galsky MD, Del Conte G, Foti S, et al. Primary analysis from DS8201-A-U105: a phase 1b, two-part, open-label study of trastuzumab deruxtecan (T-DXd) with nivolumab (nivo) in patients (pts) with HER2-expressing urothelial carcinoma (UC). J clin oncol. 2022 40; 6_suppl(6_suppl):438–438.
  • Ramjiawan RR, Griffioen AW, Duda DG. Anti-angiogenesis for cancer revisited: is there a role for combinations with immunotherapy? Angiogenesis. 2017May;20(2):185–204. Epub 2017 Mar 30. PMID: 28361267; PMCID: PMC5439974.
  • Viallard C, Larrivée B. Tumor angiogenesis and vascular normalization: alternative therapeutic targets. Angiogenesis. 2017Nov;20(4):409–426. Epub 2017 Jun 28. PMID: 28660302.
  • Palakurthi S, Kuraguchi M, Zacharek SJ, et al. The combined effect of FGFR inhibition and PD-1 blockade promotes tumor-intrinsic induction of antitumor immunity. Cancer Immunol Res. 2019Sep;7(9):1457–1471. Epub 2019 Jul 22. PMID: 31331945
  • Gerber H-P, Sapra P, Loganzo F, et al. Combining antibody–drug conjugates and immune-mediated cancer therapy: what to expect? Biochem Pharmacol. 2016 Feb 15;102:1–6. Epub 2015 Dec 11. PMID: 26686577. DOI:10.1016/j.bcp.2015.12.008
  • Yu J, Song Y, Tian W. How to select IgG subclasses in developing anti-tumor therapeutic antibodies. J Hematol Oncol. 2020May5;13(1):45. PMID: 32370812; PMCID: PMC7201658.
  • Ungaro A, Tucci M, Audisio A, et al. Antibody-drug conjugates in urothelial carcinoma: a new therapeutic opportunity moves from bench to bedside. Cells. 2022Feb25;11(5):803.
  • Herbst RS, Soria JC, Kowanetz M, et al. Predictive correlates of response to the anti-PD-L1 antibody MPDL3280A in cancer patients. Nature. 2014Nov27;515(7528):563–567.
  • Emens LA, Middleton G. The interplay of immunotherapy and chemotherapy: harnessing potential synergies. Cancer Immunol Res. 2015May;3(5):436–443. PMID: 25941355; PMCID: PMC5012642.
  • Lindberg J, Nilvebrant J, Nygren PÅ, et al. Progress and future directions with peptide-drug conjugates for targeted cancer therapy. Molecules. 2021Oct5;26(19):6042.
  • Szymczyk J, Sluzalska KD, Materla I, et al. FGF/FGFR-dependent molecular mechanisms underlying anti-cancer drug resistance. Cancers (Basel). 2021Nov18;13(22):5796.
  • Siefker-Radtke AO, Necchi A, Park SH, et al. Efficacy and safety of erdafitinib in patients with locally advanced or metastatic urothelial carcinoma: long-term follow-up of a phase 2 study. Lancet Oncol. 2022Feb;23(2):248–258. Epub 2022 Jan 11. PMID: 35030333
  • Apolo AB, Nadal R, Tomita Y, et al. Cabozantinib in patients with platinum-refractory metastatic urothelial carcinoma: an open-label, single-centre, phase 2 trial. Lancet Oncol. 2020Aug;21(8):1099–1109. Epub 2020 Jul 6. PMID: 32645282; PMCID: PMC8236112
  • Pal SK, Rosenberg JE, Hoffman-Censits JH, et al. Efficacy of BGJ398, a fibroblast growth factor receptor 1-3 inhibitor, in patients with previously treated advanced urothelial carcinoma with FGFR3 Alterations. Cancer Discov. 2018Jul;8(7):812–821. Epub 2018 May 30. PMID: 29848605; PMCID: PMC6716598
  • Petrylak DP, de Wit R, Chi KN, et al. Ramucirumab plus docetaxel versus placebo plus docetaxel in patients with locally advanced or metastatic urothelial carcinoma after platinum-based therapy (RANGE): overall survival and updated results of a randomised, double-blind, phase 3 trial. Lancet Oncol. 2020Jan;21(1):105–120. Epub 2019 Nov 18. PMID: 31753727; PMCID: PMC6946880
  • Rosenberg JE, Ballman KA, Halabi S, et al. Randomized phase III trial of gemcitabine and cisplatin with bevacizumab or placebo in patients with advanced urothelial carcinoma: results of CALGB 90601 (Alliance). J Clin Oncol. 2021Aug1;39(22):2486–2496.
  • Romero-Garcia S, Prado-Garcia H, Carlos-Reyes A. Role of DNA methylation in the resistance to therapy in solid tumors. Front Oncol. 2020Aug7;10:1152. PMID: 32850327; PMCID: PMC7426728. doi:10.3389/fonc.2020.01152.
  • Diyabalanage HV, Granda ML, Hooker JM. Combination therapy: histone deacetylase inhibitors and platinum-based chemotherapeutics for cancer. Cancer Lett. 2013Feb1;329(1):1–8. Epub 2012 Sep 29. PMID: 23032720; PMCID: PMC3546543.
  • Yi M, Niu M, Xu L, et al. Regulation of PD-L1 expression in the tumor microenvironment. J Hematol Oncol. 2021Jan7;14(1):10.
  • Suraweera A, O’Byrne KJ, Richard DJ. Combination therapy with histone deacetylase inhibitors (HDACi) for the treatment of cancer: achieving the full therapeutic potential of HDACi. Front Oncol. 2018Mar29;8:92. PMID: 29651407; PMCID: PMC5884928. doi: 10.3389/fonc.2018.00092.
  • Crabb SJ, Danson S, Catto JWF, et al. Phase I trial of DNA methyltransferase inhibitor guadecitabine combined with cisplatin and gemcitabine for Solid Malignancies Including Urothelial Carcinoma (SPIRE). Clin Cancer Res. 2021Apr1;27(7):1882–1892.
  • Adashek J, Pal SK, Chung VM, et al. Preliminary results from an ongoing phase 2a study of RX-3117, an oral nucleoside analogue to treat advanced urothelial cancer (aUC). J clin oncol. 2018;36(15_suppl):4543–4543.
  • Pili R, Quinn DI, Albany C, et al. Immunomodulation by HDAC inhibition: results from a phase Ib study with vorinostat and pembrolizumab in metastatic urothelial, renal, and prostate carcinoma patients. J clin oncol. 2019;37(15_suppl):2572–2572.
  • Zhang J, Zhou Q, Xie K, et al. Targeting WD repeat domain 5 enhances chemosensitivity and inhibits proliferation and programmed death-ligand 1 expression in bladder cancer. J Exp Clin Cancer Res. 2021Jun21;40(1):203.
  • Zehir A, Benayed R, Shah RH, et al. Mutational landscape of metastatic cancer revealed from prospective clinical sequencing of 10,000 patients. Nat Med. 2017 Jun;23(6):703–713.
  • Faraj SF, Munari E, Guner G, et al. Assessment of tumoral PD-L1 expression and intratumoral CD8+ T cells in urothelial carcinoma. Urology. 2015Mar;85(3):703.e1–6. PMID: 25733301; PMCID: PMC4695997
  • Tiller KE, Tessier PM. Advances in antibody design. Annu Rev Biomed Eng. 2015;17(1):191–216. Epub 2015 Aug 14. PMID: 26274600; PMCID: PMC5289076.
  • Salas-Benito D, Pérez-Gracia JL, Ponz-Sarvisé M, et al. Paradigms on immunotherapy combinations with chemotherapy. Cancer Discov. 2021Jun;11(6):1353–1367. Epub 2021 Mar 12. PMID: 33712487
  • Lake RA, Robinson BW. Immunotherapy and chemotherapy–a practical partnership. Nat Rev Cancer. 2005May;5(5):397–405. PMID: 15864281.
  • Ménétrier-Caux C, Ray-Coquard I, Blay JY, et al. Lymphopenia in cancer patients and its effects on response to immunotherapy: an opportunity for combination with cytokines? J Immunother Cancer. 2019Mar28;7(1):85.
  • Jiang T, Shi T, Zhang H, et al. Tumor neoantigens: from basic research to clinical applications. J Hematol Oncol. 2019Sep6;12(1):93.
  • Drago JZ, Modi S, Chandarlapaty S. Unlocking the potential of antibody-drug conjugates for cancer therapy. Nat Rev Clin Oncol. 2021Jun;18(6):327–344. Epub 2021 Feb 8. PMID: 33558752; PMCID: PMC8287784.
  • Zucali PA, Cordua N, D’Antonio F, et al. Current perspectives on immunotherapy in the peri-operative setting of muscle-infiltrating bladder cancer. Front Oncol. 2020 Oct 21;10:568279. PMID: 33194654; PMCID: PMC7609911. DOI:10.3389/fonc.2020.568279

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.