Abstract 705P
Background
Gemcitabine+cisplatin (GC) or carboplatin (GCa) are the global 1L standard of care (SOC) therapies for la/mUC; however, prognosis is poor and <50% of patients receive 1L chemotherapy. Several alternative 1L regimens are recognized by guidelines/used in practice, and new therapies are emerging. This SLR and NMA of randomized controlled trials (RCTs) compared outcomes of alternative 1L regimens with SOC to better understand the unmet need.
Methods
An SLR of phase II/III RCTs was conducted in accordance with PRISMA and NICE guidelines to identify 1L la/mUC therapies (01/2000-05/2020). Two networks were created: cisplatin (cis)-eligible/mixed eligibility and cis-ineligible. Comparative efficacy and safety were assessed via NMA under a Bayesian framework. Survival outcomes with 1L regimens vs SOC (GC/GCa) are reported.
Results
Among 1765 publications identified in the SLR, 96 representing 39 unique RCTs were selected for data extraction. Of these, 11 were included in the cis-eligible/mixed network and 6 in the cis-ineligible network. The NMA excluded therapies that were not effective or adopted in clinical practice; 3 maintenance trials were identified but excluded due to differences in study design precluding comparisons. Based on a fixed effects meta-analysis of SOC arms in each network, median overall survival (OS) was 13.2 mo (95% CI 12.4-14.0) for the cis-eligible/mixed and 9.7 mo (95% CI 6.7-12.8) for the cis-ineligible network; progression-free survival (PFS) was 6.9 (95% CI 6.3-7.4) and 5.6 mo (95% CI 4.9-6.3), respectively. OS and PFS were similar to SOC across all interventions included in the NMA (all credible intervals [CrI] crossed or were close to 1; Table). Table: 705P
HR for OS and PFS compared with SOC (GC/GCa for cis-eligible, GCa for cis-ineligible)
| Comparator | OS | PFS |
| Cis-eligible, HR (95% CrI) | ||
| ddMVAC | 0.7 (0.5, 1.0) | 0.7 (0.5, 0.9) |
| ddGC | 0.7 (0.4, 1.1) | 0.5 (0.3, 0.9) |
| Atezo+GC/GCa | 0.8 (0.7, 1.0) | 0.8 (0.7, 1.0) |
| Durva+tremelimumab | 0.9 (0.7, 1.0) | – |
| Paclitaxel+GC/GCa | 0.9 (0.7, 1.0) | 0.9 (0.7, 1.0) |
| Pembro+GC/GCa | 0.9 (0.7, 1.0) | 0.8 (0.7, 0.9) |
| MVAC | 0.9 (0.8, 1.1) | 0.9 (0.8, 1.1) |
| Pembro | 0.9 (0.8, 1.1) | – |
| Durva | 1.0 (0.8, 1.2) | – |
| Atezo | 1.0 (0.8, 1.2) | – |
| Docataxel+cis | 1.4 (1.0, 2.0) | 1.6 (1.1, 2.3) |
| Cis-ineligible, HR (95% CrI) | ||
| Durva+tremelimumab | 0.9 (0.7, 1.1) | – |
| Viniflunine+gem | 1.1 (0.6, 1.9) | 0.8 (0.4, 1.3) |
| Oxaliplatin+gem | 1.4 (0.8, 2.3) | 1.1 (0.7, 1.8) |
| M-CAVI | – | 1.0 (0.7, 1.3) |
Conclusions
Survival outcomes are similar and remain poor among existing 1L therapies for la/mUC, highlighting the continued unmet need in this largely incurable population. The impact of maintenance could not be evaluated within the framework of this 1L NMA.
Clinical trial identification
Editorial acknowledgement
Editorial support was provided by Jonathon Carthy of Curo, a division of Envision Pharma Group, and funded by Seagen Inc. and Astellas Pharma Inc.
Legal entity responsible for the study
Seagen Inc. and Astellas Pharma Inc.
Funding
Seagen Inc. and Astellas Pharma Inc.
Disclosure
L. Bloudek: Financial Interests, Personal, Other, Received support from Seagen for this research.: Seagen. Z. Hepp: Financial Interests, Personal, Full or part-time Employment: Seagen Inc.; Financial Interests, Personal, Stocks/Shares: Seagen Inc. C. McKay: Financial Interests, Personal, Full or part-time Employment: Astellas Pharma Inc. B. Devine: Financial Interests, Personal, Other, Received support from Seagen Inc. for this research: Seagen Inc. C. Derleth: Financial Interests, Personal, Full or part-time Employment: Seagen Inc.; Financial Interests, Personal, Stocks/Shares: Seagen Inc. J. Lill: Financial Interests, Personal, Full or part-time Employment: Seagen Inc.; Financial Interests, Personal, Stocks/Shares: Seagen Inc. E. Lenero: Financial Interests, Personal, Full or part-time Employment: Astellas Pharma Inc. P. Wright: Financial Interests, Personal, Full or part-time Employment: Seagen Inc.; Financial Interests, Personal, Stocks/Shares: Seagen Inc. S.D. Ramsey: Financial Interests, Personal, Other, Received support from Seagen Inc. for this research: Seagen Inc. S.D. Sullivan: Financial Interests, Personal, Other, Received support from Seagen Inc. for this research: Seagen Inc.