How Immunotherapy Has Redefined the Treatment Paradigm of Metastatic or Locally Advanced Muscle-Invasive Urothelial Bladder Carcinoma
Abstract
:Simple Summary
Abstract
1. Introduction
2. ICIs for Platinum-Pretreated Patients with Advanced UC
Trial (Year of 1st Publication) | Phase | Treatment | OS | ORR | FDA or EMA Approval * |
---|---|---|---|---|---|
Evaluation of ICI combination therapies in first-line treatment | |||||
EV-302 (2024) [11] | III | Enfortumab–vedotin + pembrolizumab vs. platinum–gemcitabine | Median OS: 31.5 vs. 16.1 mo HR: 0.46 95% CI: 0.38–0.58 (p < 0.00001) | 67.7% vs. 44.4% | FDA |
Checkmate-901 (2023) [12] | III | Nivolumab/placebo + cisplatin–gemcitabine | Median OS: 21.7 vs. 18.9 mo HR: 0.78 95% CI: 0.63–0.96 (p = 0.02) | 57.6% vs. 43.1% | FDA |
IMvigor130 (arm A vs. arm C) (2020) [13] | III | Atezolizumab/placebo + platinum–gemcitabine | Median OS: 16.1 vs. 13.4 mo NS | 48.1% vs. 44.8% | Not approved |
KEYNOTE-361 (2021) [14] | III | Pembrolizumab/placebo + platinum–gemcitabine | Median OS: 17 vs. 14.3 mo NS | 54.7% vs. 44.9% | Not approved |
GCISAVE (2024) [15] | II | Avelumab + cisplatin–gemcitabine vs. cisplatin–gemcitabine | Prematurely stopped | 79.5% vs. 59.1% | Not approved |
ICI maintenance after no progression under first-line platinum-based chemotherapy | |||||
JAVELIN Bladder 100 (2020) [16] | III | Avelumab + BSC vs. BSC | Median OS: 23.8 vs. 15.0 mo HR: 0.76 95% CI: 0.63–0.91 (p = 0.0036) | – | FDA and EMA |
Evaluation of first-line ICIs as monotherapy | |||||
KEYNOTE-361 (2021) [14] | III | Pembrolizumab vs. platinum–gemcitabine | Median OS: 15.6 vs. 14.3 mo NS | 30.3% vs. 44.9% | FDA and EMA (Cisplatin-ineligible patients only; cf. KEYNOTE-052) |
IMvigor130 (arm B vs. arm C) (2020) [13] | III | Atezolizumab vs. platinum–gemcitabine | Median OS: 15.2 vs. 13.3 mo NS | 23% vs. 44% | EMA (Cisplatin-ineligible patients only; cf. IMvigor-210) |
DANUBE (2020) [17] | III | Durvalumab + tremelimumab vs. platinum–gemcitabine Durvalumab vs. platinum–gemcitabine | Median OS: 15.1 vs. 12.1 mo NS Median OS: 14.4 vs. 12.1 mo (PD-L1 ≥ 25% population) | 36% vs. 49% 28% vs. 48% (PD-L1 ≥ 25% population) | Not approved |
IMvigor210 (2017) [18] | II | Atezolizumab in cisplatin-ineligible patients | Median OS: 15.9 mo | 23% | EMA (for tumours with PD-L1 ≥ 5%) |
KEYNOTE-052 (2017) [19] | II | Pembrolizumab in cisplatin-ineligible patients | Median OS: 11.3 mo (ITT population) Median OS: 18.5 mo (CPS ≥ 10 population) | 28.9% (ITT population) 47.3% (CPS ≥ 10 population) | FDA (for patients not eligible for any platinum-containing chemotherapy) EMA (CPS ≥ 10 population) |
Evaluation of ICIs in the second-line setting | |||||
KEYNOTE-045 (2017) [7] | III | Pembrolizumab vs. chemotherapy | Median OS: 10.3 vs. 7.4 mo HR: 0.73 95% CI: 0.58–0.91 (p = 0.002) | 21.1% vs. 11% | FDA and EMA |
IMvigor211 (2017) [10] | III | Atezolizumab vs. chemotherapy | Median OS: 11.1 vs. 10.6 mo NS (IC2/3 population) | 23% vs. 22% (IC2/3 population) | EMA (for tumours with PD-L1 ≥ 5%) |
Checkmate-275 (2017) [20] | II | Nivolumab | Median OS: 8.6 mo | 20.7% | FDA and EMA |
3. ICIs as First-Line Therapy for Advanced or Metastatic UC
3.1. ICIs as Single Agents
3.1.1. Evaluation Irrespective of Cisplatin Eligibility
3.1.2. Evaluation in Cisplatin-Ineligible Patients
3.2. ICI Maintenance after First-Line Platinum-Based Chemotherapy as a Sequential Strategy
3.3. Combination Strategies with ICI in the First-Line Setting
3.3.1. ICI–Chemotherapy Combination
3.3.2. ICI–ADC Combination
4. ICIs as Adjuvant Therapy
5. Evaluation of ICIs in the Neoadjuvant Setting
6. Evaluation of ICI in Combination with Chemoradiotherapy
7. Biomarker Selection
8. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
- van Hoogstraten, L.M.C.; Vrieling, A.; van der Heijden, A.G.; Kogevinas, M.; Richters, A.; Kiemeney, L.A. Global trends in the epidemiology of bladder cancer: Challenges for public health and clinical practice. Nat. Rev. Clin. Oncol. 2023, 20, 287–304. [Google Scholar] [CrossRef] [PubMed]
- EAU Guidelines on MIBC—DISEASE MANAGEMENT—Uroweb. Uroweb—European Association of Urology. Available online: https://uroweb.org/guidelines/muscle-invasive-and-metastatic-bladder-cancer/chapter/disease-management (accessed on 9 February 2024).
- Galsky, M.D.; Hahn, N.M.; Rosenberg, J.; Sonpavde, G.; Hutson, T.; Oh, W.K.; Dreicer, R.; Vogelzang, N.; Sternberg, C.N.; Bajorin, D.F.; et al. Treatment of patients with metastatic urothelial cancer “unfit” for Cisplatin-based chemotherapy. J. Clin. Oncol. 2011, 29, 2432–2438. [Google Scholar] [CrossRef] [PubMed]
- von der Maase, H.; Sengelov, L.; Roberts, J.T.; Ricci, S.; Dogliotti, L.; Oliver, T.; Moore, M.J.; Zimmermann, A.; Arning, M. 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. 2005, 23, 4602–4608. [Google Scholar] [CrossRef] [PubMed]
- De Santis, M.; Bellmunt, J.; Mead, G.; Kerst, J.M.; Leahy, M.; Maroto, P.; Gil, T.; Marreaud, S.; Daugaard, G.; Skoneczna, I.; 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. 2012, 30, 191–199. [Google Scholar] [CrossRef] [PubMed]
- Loriot, Y.; Matsubara, N.; Park, S.H.; Huddart, R.A.; Burgess, E.F.; Houede, N.; Banek, S.; Guadalupi, V.; Ku, J.H.; Valderrama, B.P.; et al. Erdafitinib or Chemotherapy in Advanced or Metastatic Urothelial Carcinoma. N. Engl. J. Med. 2023, 389, 1961–1971. [Google Scholar] [CrossRef] [PubMed]
- Bellmunt, J.; de Wit, R.; Vaughn, D.J.; Fradet, Y.; Lee, J.-L.; Fong, L.; Vogelzang, N.J.; Climent, M.A.; Petrylak, D.P.; Choueiri, T.K.; et al. Pembrolizumab as Second-Line Therapy for Advanced Urothelial Carcinoma. N. Engl. J. Med. 2017, 376, 1015–1026. [Google Scholar] [CrossRef] [PubMed]
- Balar, A.V.; Castellano, D.E.; Grivas, P.; Vaughn, D.J.; Powles, T.; Vuky, J.; Fradet, Y.; Lee, J.-L.; Fong, L.; Vogelzang, N.J.; et al. Efficacy and safety of pembrolizumab in metastatic urothelial carcinoma: Results from KEYNOTE-045 and KEYNOTE-052 after up to 5 years of follow-up. Ann. Oncol. 2023, 34, 289–299. [Google Scholar] [CrossRef] [PubMed]
- Rosenberg, J.E.; Hoffman-Censits, J.; Powles, T.; van der Heijden, M.S.; Balar, A.V.; Necchi, A.; Dawson, N.; O’Donnell, P.H.; Balmanoukian, A.; Loriot, Y.; 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 2016, 387, 1909–1920. [Google Scholar] [CrossRef]
- Powles, T.; Durán, I.; van der Heijden, M.S.; Loriot, Y.; Vogelzang, N.J.; De Giorgi, U.; Oudard, S.; Retz, M.M.; Castellano, D.; Bamias, A.; et al. Atezolizumab versus chemotherapy in patients with platinum-treated locally advanced or metastatic urothelial carcinoma (IMvigor211): A multicentre, open-label, phase 3 randomised controlled trial. Lancet 2018, 391, 748–757. [Google Scholar] [CrossRef]
- Powles, T.; Valderrama, B.P.; Gupta, S.; Bedke, J.; Kikuchi, E.; Hoffman-Censits, J.; Iyer, G.; Vulsteke, C.; Park, S.H.; Shin, S.J.; et al. Enfortumab Vedotin and Pembrolizumab in Untreated Advanced Urothelial Cancer. N. Engl. J. Med. 2024, 390, 875–888. [Google Scholar] [CrossRef]
- van der Heijden, M.S.; Sonpavde, G.; Powles, T.; Necchi, A.; Burotto, M.; Schenker, M.; Sade, J.P.; Bamias, A.; Beuzeboc, P.; Bedke, J.; et al. Nivolumab plus Gemcitabine-Cisplatin in Advanced Urothelial Carcinoma. N. Engl. J. Med. 2023, 389, 1778–1789. [Google Scholar] [CrossRef] [PubMed]
- Galsky, M.D.; Arija, J.Á.A.; Bamias, A.; Davis, I.D.; De Santis, M.; Kikuchi, E.; Garcia-Del-Muro, X.; De Giorgi, U.; Mencinger, M.; Izumi, K.; et al. Atezolizumab with or without chemotherapy in metastatic urothelial cancer (IMvigor130): A multicentre, randomised, placebo-controlled phase 3 trial. Lancet 2020, 395, 1547–1557. [Google Scholar] [CrossRef] [PubMed]
- Powles, T.; Csőszi, T.; Özgüroğlu, M.; Matsubara, N.; Géczi, L.; Cheng, S.Y.-S.; Fradet, Y.; Oudard, S.; Vulsteke, C.; Morales Barrera, R.; 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. 2021, 22, 931–945. [Google Scholar] [CrossRef] [PubMed]
- Gross-Goupil, M.; Frison, E.; Roubaud, G.; Flechon, A.; Calcagno, F.; Rolland, F.; Joly, F.; Raymond, A.-A.; Chotard, G.; Barthelemy, P.; et al. GCISAVE: A non-comparative randomized phase II study of combination of gemcitabine cisplatin (GCis) +/- avelumab (A) in 1st line treatment for locally advanced or metastatic urothelial bladder carcinoma (MUBC)—GETUG AFU V07. J. Clin. Oncol. 2024, 42, 637. [Google Scholar] [CrossRef]
- Powles, T.; Park, S.H.; Voog, E.; Caserta, C.; Valderrama, B.P.; Gurney, H.; Kalofonos, H.; Radulović, S.; Demey, W.; Ullén, A.; et al. Avelumab Maintenance Therapy for Advanced or Metastatic Urothelial Carcinoma. N. Engl. J. Med. 2020, 383, 1218–1230. [Google Scholar] [CrossRef] [PubMed]
- Powles, T.; van der Heijden, M.S.; Castellano, D.; Galsky, M.D.; Loriot, Y.; Petrylak, D.P.; Ogawa, O.; Park, S.H.; Lee, J.-L.; De Giorgi, U.; 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, 21, 1574–1588. [Google Scholar] [CrossRef] [PubMed]
- Balar, A.V.; Galsky, M.D.; Rosenberg, J.E.; Powles, T.; Petrylak, D.P.; Bellmunt, J.; Loriot, Y.; Necchi, A.; Hoffman-Censits, J.; Perez-Gracia, J.L.; 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 2017, 389, 67–76. [Google Scholar] [CrossRef] [PubMed]
- Balar, A.V.; Castellano, D.; O’Donnell, P.H.; Grivas, P.; Vuky, J.; Powles, T.; Plimack, E.R.; Hahn, N.M.; de Wit, R.; Pang, L.; 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. 2017, 18, 1483–1492. [Google Scholar] [CrossRef] [PubMed]
- Sharma, P.; Retz, M.; Siefker-Radtke, A.; Baron, A.; Necchi, A.; Bedke, J.; Plimack, E.R.; Vaena, D.; Grimm, M.-O.; Bracarda, S.; et al. Nivolumab in metastatic urothelial carcinoma after platinum therapy (CheckMate 275): A multicentre, single-arm, phase 2 trial. Lancet Oncol. 2017, 18, 312–322. [Google Scholar] [CrossRef]
- Galsky, M.D.; Saci, A.; Szabo, P.M.; Han, G.C.; Grossfeld, G.; Collette, S.; Siefker-Radtke, A.; Necchi, A.; Sharma, P. Nivolumab in Patients with Advanced Platinum-Resistant Urothelial Carcinoma: Efficacy, Safety, and Biomarker Analyses with Extended Follow-up from CheckMate 275. Clin. Cancer Res. 2020, 26, 5120–5128. [Google Scholar] [CrossRef]
- Patel, M.R.; Ellerton, J.; Infante, J.R.; Agrawal, M.; Gordon, M.; Aljumaily, R.; Britten, C.D.; Dirix, L.; Lee, K.-W.; Taylor, M.; 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. 2018, 19, 51–64. [Google Scholar] [CrossRef] [PubMed]
- Powles, T.; O’Donnell, P.H.; Massard, C.; Arkenau, H.-T.; Friedlander, T.W.; Hoimes, C.J.; Lee, J.L.; Ong, M.; Sridhar, S.S.; Vogelzang, N.J.; 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. 2017, 3, e172411. [Google Scholar] [CrossRef] [PubMed]
- AstraZeneca Withdraws Durvalumab Indication for Previously Treated Locally Advanced or Metastatic Bladder Cancer. Cancer Network. 2021. Available online: https://www.cancernetwork.com/view/astrazeneca-withdraws-durvalumab-indication-for-previously-treated-locally-advanced-or-metastatic-bladder-cancer (accessed on 21 January 2024).
- Bladder Cancer: ESMO Clinical Practice Guideline for Diagnosis, Treatment and Follow-Up☆—Annals of Oncology. Available online: https://www.annalsofoncology.org/article/S0923-7534(21)04827-4/fulltext (accessed on 21 March 2024).
- Bamias, A.; Davis, I.D.; Galsky, M.D.; Arranz, J.Á.; Kikuchi, E.; Grande, E.; del Muro, X.G.; Park, S.H.; Giorgi, U.D.; Alekseev, B.; et al. Atezolizumab monotherapy versus chemotherapy in untreated locally advanced or metastatic urothelial carcinoma (IMvigor130): Final overall survival analysis from a randomised, controlled, phase 3 study. Lancet Oncol. 2024, 25, 46–61. [Google Scholar] [CrossRef] [PubMed]
- Galsky, M.D.; Chen, G.J.; Oh, W.K.; Bellmunt, J.; Roth, B.J.; Petrioli, R.; Dogliotti, L.; Dreicer, R.; Sonpavde, G. Comparative effectiveness of cisplatin-based and carboplatin-based chemotherapy for treatment of advanced urothelial carcinoma. Ann. Oncol. 2012, 23, 406–410. [Google Scholar] [CrossRef] [PubMed]
- Bamias, A.; Tzannis, K.; Harshman, L.C.; Crabb, S.J.; Wong, Y.-N.; Pal, S.K.; Giorgi, U.D.; Ladoire, S.; Agarwal, N.; Yu, E.Y.; 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. 2018, 29, 361–369. [Google Scholar] [CrossRef] [PubMed]
- Powles, T.; Park, S.H.; Caserta, C.; Valderrama, B.P.; Gurney, H.; Ullén, A.; Loriot, Y.; Sridhar, S.S.; Sternberg, C.N.; Bellmunt, J.; et al. Avelumab First-Line Maintenance for Advanced Urothelial Carcinoma: Results From the JAVELIN Bladder 100 Trial After ≥2 Years of Follow-Up. J. Clin. Oncol. 2023, 41, 3486–3492. [Google Scholar] [CrossRef] [PubMed]
- Sridhar, S.S.; Powles, T.; Durán, M.Á.C.; Park, S.H.; Massari, F.; Thiery-Vuillemin, A.; Valderrama, B.P.; Ullén, A.; Tsuchiya, N.; Aragon-Ching, J.B.; et al. Avelumab First-line Maintenance for Advanced Urothelial Carcinoma: Analysis from JAVELIN Bladder 100 by Duration of First-line Chemotherapy and Interval Before Maintenance. Eur. Urol. 2024, 85, 154–163. [Google Scholar] [CrossRef] [PubMed]
- Grivas, P.; Grande, E.; Davis, I.D.; Moon, H.H.; Grimm, M.-O.; Gupta, S.; Barthélémy, P.; Thibault, C.; Guenther, S.; Hanson, S.; et al. Avelumab first-line maintenance treatment for advanced urothelial carcinoma: Review of evidence to guide clinical practice. ESMO Open 2023, 8, 102050. [Google Scholar] [CrossRef] [PubMed]
- Barthelemy, P.; Loriot, Y.; Voog, E.; Eymard, J.C.; Ravaud, A.; Flechon, A.; Abraham Jaillon, C.; Chasseray, M.; Lorgis, V.; Hilgers, W.; et al. Full analysis from AVENANCE: A real-world study of avelumab first-line (1L) maintenance treatment in patients (pts) with advanced urothelial carcinoma (aUC). J. Clin. Oncol. 2023, 41, 471. [Google Scholar] [CrossRef]
- Barthelemy, P.; Loriot, Y.; Thibault, C.; Gross-Goupil, M.; Eymard, J.C.; Voog, E.; Abraham Jaillon, C.; Le Moulec, S.; Chasseray, M.; Gobert, A.; et al. Updated results from AVENANCE: Real-world effectiveness of avelumab first-line maintenance (1LM) in patients (pts) with advanced urothelial carcinoma (aUC) and analysis of subsequent treatment. J. Clin. Oncol. 2024, 42, 561. [Google Scholar] [CrossRef]
- Grivas, P.; Barata, P.C.; Moon, H.; Hutson, T.E.; Gupta, S.; Sternberg, C.N.; Pickard, A.S.; Dave, V.; Han, N.; Shillington, A.C.; et al. PATRIOT II: An ambispective, observational, multicenter, 2-cohort study of avelumab (Ave) first-line maintenance (1LM) in locally advanced/metastatic urothelial carcinoma (la/mUC) in the United States. J. Clin. Oncol. 2022, 40, TPS578. [Google Scholar] [CrossRef]
- Grande, E.; Arranz, J.Á.; Santis, M.D.; Bamias, A.; Kikuchi, E.; del Muro, X.G.; Park, S.H.; Giorgi, U.D.; Alekseev, B.; Mencinger, M.; et al. Atezolizumab plus chemotherapy versus placebo plus chemotherapy in untreated locally advanced or metastatic urothelial carcinoma (IMvigor130): Final overall survival analysis results from a randomised, controlled, phase 3 study. Lancet Oncol. 2024, 25, 29–45. [Google Scholar] [CrossRef]
- Grande, E.; Bamias, A.; Galsky, M.D.; Kikuchi, E.; Davis, I.D.; Arranz, J.A.; Rezazadeh, A.; Garcia del Muro, X.; Park, S.H.; De Giorgi, U.; et al. Overall survival (OS) by response to first-line (1L) induction treatment with atezolizumab (atezo) + platinum/gemcitabine (plt/gem) vs placebo + plt/gem in patients (pts) with metastatic urothelial carcinoma (mUC): Updated data from the IMvigor130 OS final analysis. J. Clin. Oncol. 2023, 41, 4503. [Google Scholar] [CrossRef]
- Müller, P.; Martin, K.; Theurich, S.; Schreiner, J.; Savic, S.; Terszowski, G.; Lardinois, D.; Heinzelmann-Schwarz, V.A.; Schlaak, M.; Kvasnicka, H.-M.; et al. Microtubule-depolymerizing agents used in antibody-drug conjugates induce antitumor immunity by stimulation of dendritic cells. Cancer Immunol. Res. 2014, 2, 741–755. [Google Scholar] [CrossRef] [PubMed]
- Challita-Eid, P.M.; Satpayev, D.; Yang, P.; An, Z.; Morrison, K.; Shostak, Y.; Raitano, A.; Nadell, R.; Liu, W.; Lortie, D.R.; et al. Enfortumab Vedotin Antibody-Drug Conjugate Targeting Nectin-4 Is a Highly Potent Therapeutic Agent in Multiple Preclinical Cancer Models. Cancer Res. 2016, 76, 3003–3013. [Google Scholar] [CrossRef]
- Heiser, R.A.; Cao, A.T.; Zeng, W.; Ulrich, M.; Younan, P.; Anderson, M.E.; Trueblood, E.S.; Jonas, M.; Thurman, R.; Law, C.-L.; et al. Brentuximab Vedotin–Driven Microtubule Disruption Results in Endoplasmic Reticulum Stress Leading to Immunogenic Cell Death and Antitumor Immunity. Mol. Cancer Ther. 2024, 23, 68–83. [Google Scholar] [CrossRef] [PubMed]
- Hoimes, C.J.; Flaig, T.W.; Milowsky, M.I.; Friedlander, T.W.; Bilen, M.A.; Gupta, S.; Srinivas, S.; Merchan, J.R.; McKay, R.R.; Petrylak, D.P.; et al. Enfortumab vedotin plus pembrolizumab in previously untreated advanced urothelial cancer. J. Clin. Oncol. 2023, 41, 22–31. [Google Scholar] [CrossRef] [PubMed]
- O’Donnell, P.H.; Milowsky, M.I.; Petrylak, D.P.; Hoimes, C.J.; Flaig, T.W.; Mar, N.; Moon, H.H.; Friedlander, T.W.; McKay, R.R.; Bilen, M.A.; et al. Enfortumab Vedotin with or without Pembrolizumab in Cisplatin-Ineligible Patients with Previously Untreated Locally Advanced or Metastatic Urothelial Cancer. J. Clin. Oncol. 2023, 41, 4107–4117. [Google Scholar] [CrossRef] [PubMed]
- Van Der Heijden, M.S.; Powles, T.; Gupta, S.; Bedke, J.; Kikuchi, E.; De Wit, R.; Galsky, M.D.; Duran, I.; Necchi, A.; Retz, M.; et al. Enfortumab vedotin (EV) in combination with pembrolizumab (P) versus chemotherapy in previously untreated locally advanced metastatic urothelial carcinoma (la/mUC): Subgroup analyses results from EV-302, a phase 3 global study. J. Clin. Oncol. 2024, 42, LBA530. [Google Scholar] [CrossRef]
- U.S. Food and Drug Administration. FDA Approves Enfortumab Vedotin-Ejfv with Pembrolizumab for Locally Advanced or Metastatic Urothelial Cancer; FDA: Silver Spring, MD, USA, 2023.
- Advanced Bladder Cancer (ABC) Meta-Analysis Collaborators Group. Adjuvant Chemotherapy for Muscle-invasive Bladder Cancer: A Systematic Review and Meta-analysis of Individual Participant Data from Randomised Controlled Trials. Eur. Urol. 2022, 81, 50–61. [Google Scholar] [CrossRef]
- Bajorin, D.F.; Witjes, J.A.; Gschwend, J.E.; Schenker, M.; Valderrama, B.P.; Tomita, Y.; Bamias, A.; Lebret, T.; Shariat, S.F.; Park, S.H.; et al. Adjuvant Nivolumab versus Placebo in Muscle-Invasive Urothelial Carcinoma. N. Engl. J. Med. 2021, 384, 2102–2114. [Google Scholar] [CrossRef] [PubMed]
- Galsky, M.D.; Witjes, A.A.; Gschwend, J.E.; Schenker, M.; Valderrama, B.P.; Tomita, Y.; Bamias, A.; Lebret, T.; Shariat, S.F.; Park, S.H.; et al. Extended follow-up results from the CheckMate 274 trial. J. Clin. Oncol. 2023, 41, LBA443. [Google Scholar] [CrossRef]
- Bellmunt, J.; Hussain, M.; Gschwend, J.E.; Albers, P.; Oudard, S.; Castellano, D.; Daneshmand, S.; Nishiyama, H.; Majchrowicz, M.; Degaonkar, V.; et al. Adjuvant atezolizumab versus observation in muscle-invasive urothelial carcinoma (IMvigor010): A multicentre, open-label, randomised, phase 3 trial. Lancet Oncol. 2021, 22, 525–537. [Google Scholar] [CrossRef] [PubMed]
- Powles, T.; Assaf, Z.J.; Degaonkar, V.; Grivas, P.; Hussain, M.; Oudard, S.; Gschwend, J.E.; Albers, P.; Castellano, D.; Nishiyama, H.; et al. Updated Overall Survival by Circulating Tumor DNA Status from the Phase 3 IMvigor010 Trial: Adjuvant Atezolizumab Versus Observation in Muscle-invasive Urothelial Carcinoma. Eur. Urol. 2024, 85, 114–122. [Google Scholar] [CrossRef] [PubMed]
- Jackson-Spence, F.; Toms, C.; O’Mahony, L.F.; Choy, J.; Flanders, L.; Szabados, B.; Powles, T. IMvigor011: A study of adjuvant atezolizumab in patients with high-risk MIBC who are ctDNA+ post-surgery. Future Oncol. 2023, 19, 509–515. [Google Scholar] [CrossRef] [PubMed]
- Apolo, A.B.; Ballman, K.V.; Sonpavde, G.P.; Berg, S.A.; Kim, W.Y.; Parikh, R.A.; Teo, M.Y.; Sweis, R.F.; Geynisman, D.M.; Grivas, P.; et al. AMBASSADOR Alliance A031501: Phase III randomized adjuvant study of pembrolizumab in muscle-invasive and locally advanced urothelial carcinoma (MIUC) vs observation. J. Clin. Oncol. 2024, 42, LBA531. [Google Scholar] [CrossRef]
- Pfister, C.; Gravis, G.; Fléchon, A.; Soulié, M.; Guy, L.; Laguerre, B.; Mottet, N.; Joly, F.; Allory, Y.; Harter, V.; et al. Randomized Phase III Trial of Dose-dense Methotrexate, Vinblastine, Doxorubicin, and Cisplatin, or Gemcitabine and Cisplatin as Perioperative Chemotherapy for Patients with Muscle-invasive Bladder Cancer. Analysis of the GETUG/AFU V05 VESPER Trial Secondary Endpoints: Chemotherapy Toxicity and Pathological Responses. Eur. Urol. 2021, 79, 214–221. [Google Scholar] [CrossRef] [PubMed]
- Szabados, B.; Kockx, M.; Assaf, Z.J.; Dam, P.-J.; van Rodriguez-Vida, A.; Duran, I.; Crabb, S.J.; Heijden, M.S.V.D.; Pous, A.F.; Gravis, G.; et al. Final Results of Neoadjuvant Atezolizumab in Cisplatin-ineligible Patients with Muscle-invasive Urothelial Cancer of the Bladder. Eur. Urol. 2022, 82, 212–222. [Google Scholar] [CrossRef]
- Necchi, A.; Anichini, A.; Raggi, D.; Briganti, A.; Massa, S.; Lucianò, R.; Colecchia, M.; Giannatempo, P.; Mortarini, R.; Bianchi, M.; 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. 2018, 36, 3353–3360. [Google Scholar] [CrossRef]
- Powles, T.; Kockx, M.; Rodriguez-Vida, A.; Duran, I.; Crabb, S.J.; Van Der Heijden, M.S.; Szabados, B.; Pous, A.F.; Gravis, G.; Herranz, U.A.; et al. Clinical efficacy and biomarker analysis of neoadjuvant atezolizumab in operable urothelial carcinoma in the ABACUS trial. Nat. Med. 2019, 25, 1706–1714. [Google Scholar] [CrossRef]
- Rose, T.L.; Harrison, M.R.; Deal, A.M.; Ramalingam, S.; Whang, Y.E.; Brower, B.; Dunn, M.; Osterman, C.K.; Heiling, H.M.; Bjurlin, M.A.; 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. 2021, 39, 3140–3148. [Google Scholar] [CrossRef]
- Funt, S.A.; Lattanzi, M.; Whiting, K.; Al-Ahmadie, H.; Quinlan, C.; Teo, M.Y.; Lee, C.-H.; Aggen, D.; Zimmerman, D.; McHugh, D.; 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. 2022, 40, 1312–1322. [Google Scholar] [CrossRef]
- Galsky, M.D.; Daneshmand, S.; Izadmehr, S.; Gonzalez-Kozlova, E.; Chan, K.G.; Lewis, S.; Achkar, B.E.; Dorff, T.B.; Cetnar, J.P.; Neil, B.O.; et al. Gemcitabine and cisplatin plus nivolumab as organ-sparing treatment for muscle-invasive bladder cancer: A phase 2 trial. Nat. Med. 2023, 29, 2825–2834. [Google Scholar] [CrossRef]
- Siefker-Radtke, A.O.; Steinberg, G.; Bedke, J.; Nishiyama, H.; Martin, J.; Kataria, R.; Frenkl, T.L.; Hoimes, C.J. 988TiP—KEYNOTE-866: Phase III study of perioperative pembrolizumab (pembro) or placebo (pbo) in combination with neoadjuvant chemotherapy in cisplatin (cis)-eligible patients (pts) with muscle-invasive bladder cancer (MIBC). Ann. Oncol. 2019, 30, v401. [Google Scholar] [CrossRef]
- Sonpavde, G.; Necchi, A.; Gupta, S.; Steinberg, G.D.; Gschwend, J.E.; Van Der Heijden, M.S.; Garzon, N.; Ibrahim, M.; Raybold, B.; Liaw, D.; et al. ENERGIZE: A Phase III study of neoadjuvant chemotherapy alone or with nivolumab with/without linrodostat mesylate for muscle-invasive bladder cancer. Future Oncol. 2020, 16, 4359–4368. [Google Scholar] [CrossRef] [PubMed]
- Powles, T.; Meeks, J.J.; Galsky, M.D.; Van Der Heijden, M.S.; Nishiyama, H.; Al-Ahmadie, H.A.; Goluboff, E.T.; Hois, S.; Donegan, S.E.; Williams, V.; et al. A phase III, randomized, open-label, multicenter, global study of efficacy and safety of durvalumab in combination with gemcitabine plus cisplatin for neoadjuvant treatment followed by durvalumab alone for adjuvant treatment in muscle-invasive bladder cancer (NIAGARA). J. Clin. Oncol. 2021, 39, TPS505. [Google Scholar] [CrossRef]
- Grivas, P.; Van Der Heijden, M.S.; Necchi, A.; Siefker-Radtke, A.O.; Cutuli, H.; Qureshi, A.H.; Kreiser, S.; Hodari, M.; Ravimohan, S.; Zakharia, Y. PIVOT IO 009: A phase 3, randomized study of neoadjuvant and adjuvant nivolumab (NIVO) plus bempegaldesleukin (BEMPEG; NKTR-214) versus NIVO alone versus standard of care (SOC) in patients (pts) with muscle-invasive bladder cancer (MIBC) who are cisplatin (cis)-ineligible. J. Clin. Oncol. 2022, 40, TPS596. [Google Scholar] [CrossRef]
- van Hattum, J.W.; de Ruiter, B.-M.; Oddens, J.R.; Hulshof, M.C.C.M.; de Reijke, T.M.; Bins, A.D. Bladder-Sparing Chemoradiotherapy Combined with Immune Checkpoint Inhibition for Locally Advanced Urothelial Bladder Cancer—A Review. Cancers 2021, 14, 38. [Google Scholar] [CrossRef]
- Wu, C.-T.; Chen, W.-C.; Chang, Y.-H.; Lin, W.-Y.; Chen, M.-F. The role of PD-L1 in the radiation response and clinical outcome for bladder cancer. Sci. Rep. 2016, 6, 19740. [Google Scholar] [CrossRef] [PubMed]
- Fujii, Y.; Heijden, M.S.V.D.; Weickhardt, A.J.; James, N.D.; Shariat, S.F.; Michalski, J.M.; Imai, K.; Fang, X.; Kapadia, E.; Shore, N.D. Phase 3 KEYNOTE-992 study of pembrolizumab plus chemoradiotherapy versus placebo plus chemoradiotherapy in patients with muscle-invasive bladder cancer (MIBC). J. Clin. Oncol. 2024, 42, TPS720. [Google Scholar] [CrossRef]
- Meeks, J.J.; Black, P.C.; Galsky, M.; Grivas, P.; Hahn, N.M.; Hussain, S.A.; Milowsky, M.I.; Steinberg, G.D.; Svatek, R.S.; Rosenberg, J.E. Checkpoint Inhibitors in Urothelial Carcinoma—Future Directions and Biomarker Selection. Eur. Urol. 2023, 84, 473–483. [Google Scholar] [CrossRef] [PubMed]
- Graf, R.P.; Fisher, V.; Huang, R.S.P.; Hamdani, O.; Gjoerup, O.V.; Stanke, J.; Creeden, J.; Levy, M.A.; Oxnard, G.R.; Gupta, S. Tumor Mutational Burden as a Predictor of First-Line Immune Checkpoint Inhibitor Versus Carboplatin Benefit in Cisplatin-Unfit Patients with Urothelial Carcinoma. JCO Precis. Oncol. 2022, 6, e2200121. [Google Scholar] [CrossRef] [PubMed]
- Ferreiro-Pantín, M.; Anido-Herranz, U.; Betancor, Y.Z.; Cebey-López, V.; León-Mateos, L.; García-González, J.; García-Acuña, S.M.; Fernández-Díaz, N.; Tubio, J.M.C.; López-López, R.; et al. Clinical, molecular, and immune correlates of the Immunotherapy Response Score in patients with advanced urothelial carcinoma under atezolizumab monotherapy: Analysis of the phase II IMvigor210 trial. ESMO Open 2023, 8, 101611. [Google Scholar] [CrossRef] [PubMed]
- Sarfaty, M.; Golkaram, M.; Funt, S.A.; Al-Ahmadie, H.; Kaplan, S.; Song, F.; Regazzi, A.; Makarov, V.; Kuo, F.; Ostrovnaya, I.; et al. Novel Genetic Subtypes of Urothelial Carcinoma with Differential Outcomes on Immune Checkpoint Blockade. J. Clin. Oncol. 2023, 41, 3225–3235. [Google Scholar] [CrossRef]
- Powles, T.; Bellmunt, J.; Comperat, E.; Santis, M.D.; Huddart, R.; Loriot, Y.; Necchi, A.; Valderrama, B.P.; Ravaud, A.; Shariat, S.F.; et al. ESMO Clinical Practice Guideline interim update on first-line therapy in advanced urothelial carcinoma. Ann. Oncol. 2024, in press. [Google Scholar] [CrossRef]
Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content. |
© 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Share and Cite
Larroquette, M.; Lefort, F.; Domblides, C.; Héraudet, L.; Robert, G.; Ravaud, A.; Gross-Goupil, M. How Immunotherapy Has Redefined the Treatment Paradigm of Metastatic or Locally Advanced Muscle-Invasive Urothelial Bladder Carcinoma. Cancers 2024, 16, 1780. https://doi.org/10.3390/cancers16091780
Larroquette M, Lefort F, Domblides C, Héraudet L, Robert G, Ravaud A, Gross-Goupil M. How Immunotherapy Has Redefined the Treatment Paradigm of Metastatic or Locally Advanced Muscle-Invasive Urothelial Bladder Carcinoma. Cancers. 2024; 16(9):1780. https://doi.org/10.3390/cancers16091780
Chicago/Turabian StyleLarroquette, Mathieu, Félix Lefort, Charlotte Domblides, Luc Héraudet, Grégoire Robert, Alain Ravaud, and Marine Gross-Goupil. 2024. "How Immunotherapy Has Redefined the Treatment Paradigm of Metastatic or Locally Advanced Muscle-Invasive Urothelial Bladder Carcinoma" Cancers 16, no. 9: 1780. https://doi.org/10.3390/cancers16091780
APA StyleLarroquette, M., Lefort, F., Domblides, C., Héraudet, L., Robert, G., Ravaud, A., & Gross-Goupil, M. (2024). How Immunotherapy Has Redefined the Treatment Paradigm of Metastatic or Locally Advanced Muscle-Invasive Urothelial Bladder Carcinoma. Cancers, 16(9), 1780. https://doi.org/10.3390/cancers16091780