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
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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