Related Experiment Video
Updated: Oct 12, 2025
Induction of Invasive Transitional Cell Bladder Carcinoma in Immune Intact Human MUC1 Transgenic Mice: A Model for Immunotherapy Development
Published on: October 30, 2013
Immuno-oncology therapy in metastatic bladder cancer: A systematic review and network meta-analysis
Francesco Chierigo1, Mike Wenzel2, Christoph Würnschimmel3
1Department of Surgical and Diagnostic Integrated Sciences (DISC), University of Genova, Genova, Italy; Cancer Prognostics and Health Outcomes Unit, Division of Urology, University of Montréal Health Center, Montréal, Québec, Canada.
Context:
Three first line and three second-line clinical trials tested the effect of immunotherapy (IO) relative to standard chemotherapy (CT) on overall survival. However, network meta-analysis-based comparisons have not yet been presented. We addressed this void.
Objective:
To provide comparisons of overall survival (OS), progression-free survival (PFS), complete response (CR), partial response (PR), stable disease (SD), objective response rates (ORR), disease control rates (DCR) and adverse events (AEs) associated with 1st and 2nd line IO-based regimens.
Materials And Methods:
PubMed was searched for phase III randomized controlled trials from 2016 to 2021, including conference abstracts. We identified three first line [IMvigor130 (atezolizumab + CT vs atezolizumab vs CT), DANUBE (durvalumab vs durvalumab + tremelimumab vs CT), and KEYNOTE-361 (pembrolizumab + CT vs pembrolizumab vs CT)] and two second line [KEYNOTE-045 (pembrolizumab vs CT) and IMvigor211 (atezolizumab vs CT)] RCTs.
Results:
Overall, 3255 and 1452 patients were respectively included in the first- and second-line settings. In 1st line setting, compared with CT, no IO-based regimen exhibited survival benefit. However, all exclusive IO regimens resulted in lower rates of grade 3+ AEs. In 2nd line setting, compared with CT, only pembrolizumab improved OS benefit. Conversely, atezolizumab only showed OS benefit in exploratory analyses. Compared to second-line CT, no experimental regimen (atezolizumab or pembrolizumab) exhibited statistically significant ORR benefit. Both pembrolizumab and atezolizumab resulted in lower rates of grade 3+ AEs compared to 2nd line CT.
Conclusions:
In metastatic UC, IO-based regimens do not hold a survival benefit relative to CT in 1st line setting. However, pembrolizumab holds a survival benefit in 2nd line compared to CT. Several IO-based clinical trials are ongoing and will provide more and possibly better treatment alternatives for locally advanced and metastatic UC.
Insights
Immunotherapy (IO) did not improve survival versus chemotherapy in first-line metastatic urothelial carcinoma (UC). Pembrolizumab showed survival benefit in second-line UC, with fewer adverse events compared to chemotherapy.
Area of Science:
- Oncology
- Clinical Trials
- Immunotherapy
Background:
- Standard chemotherapy (CT) is a common treatment for urothelial carcinoma (UC).
- Immunotherapy (IO) has emerged as a promising treatment modality.
- Limited comparative data exists for first- and second-line IO-based regimens versus CT.
Purpose of the Study:
- To compare overall survival (OS), progression-free survival (PFS), and response rates (ORR) of first- and second-line IO-based regimens against standard chemotherapy (CT).
- To evaluate adverse events (AEs) associated with these treatment regimens.
Main Methods:
- A systematic search of PubMed for phase III randomized controlled trials (RCTs) from 2016-2021 was conducted.
- Included trials evaluated first-line and second-line immunotherapy regimens in metastatic UC.
- Data from 3255 patients (first-line) and 1452 patients (second-line) were analyzed.
Main Results:
- In the first-line setting, no IO-based regimen demonstrated a survival benefit over CT, though exclusive IO regimens had lower grade 3+ AEs.
- In the second-line setting, pembrolizumab improved OS compared to CT; atezolizumab showed benefit only in exploratory analyses.
- No experimental regimen showed a statistically significant ORR benefit over second-line CT, but both pembrolizumab and atezolizumab had lower grade 3+ AEs.
Conclusions:
- IO-based regimens do not offer a survival advantage over CT in the first-line treatment of metastatic UC.
- Pembrolizumab demonstrates a survival benefit in the second-line setting for metastatic UC compared to CT.
- Ongoing clinical trials are expected to provide further treatment alternatives for advanced UC.
Related Concept Videos
01:27Tumor Immunotherapy
02:49Cancer Therapies
However, cancer treatments can pose several challenges, as therapies used to kill cancer cells are generally also toxic to normal cells. Moreover, cancer cells mutate rapidly and can develop resistance to chemical agents or radiation therapy. Besides, all types of cancer cells may not respond to the same therapy. Some cancer cells respond to one...
02:57Targeted Cancer Therapies
There are several types of targeted therapies against...