Abstract
Introduction: Until recently, systemic chemotherapy was the only option for treating bladder cancer and outcomes remained dismal. After a long gap of no progress for 40 years, immunotherapy with checkpoint inhibitors (PDL1 and PD1) has revolutionized the treatment paradigm of bladder cancer, with five approved agents to treat platinum-refractory bladder cancer since the first approval of atezolizumab in May 2016. Methods: This review summarizes the most recent data on approved checkpoint inhibitors currently used in management of advanced bladder cancer. Early-and late-phase trials of the five checkpoint inhibitors (pembrolizumab, nivolumab, atezolizumab, durvalumab, and avelumab) in advanced bladder cancer are reviewed in detail. This review also describes the potential application of PD1/PDL1 inhibitors in adjuvant and neoadjuvant settings and non-muscle-invasive bladder cancer, as well as with radiation in muscle-invasive bladder cancer treatment. The role of PDL1 and tumor-mutation burden and clinical considerations in choosing a particular immunotherapy are also discussed. Results: The approved checkpoint inhibitors (PD1 and PDL1 inhibitors) have similar efficacy and safety profiles in metastatic platinum-refractory bladder cancer, but they vary in dose and frequency and cost burden. However, only pembrolizumab has shown superiority over standard chemotherapy in a randomized Phase III setting so far. In addition, in the first-line setting for cisplatin-ineligible patients, both pembrolizumab and atezolizumab are US Food and Drug Administration-approved and well tolerated. There is a lack of consensus on the utility of testing for PDL1 as a predictive biomarker, as patients with no PDL1 expression also derive some clinical benefit. Tumor-mutation burden is another predictive biomarker, but needs further validation. Conclusion: Immunotherapy has offered a glimmer of hope to patients with bladder cancer. The current landscape is rapidly evolving, with novel immunotherapy-combination trials to improve outcomes further and evaluate predictive biomarkers to help identify patients most likely to benefit from such therapies.
Original language | English (US) |
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Pages (from-to) | 5973-5989 |
Number of pages | 17 |
Journal | OncoTargets and Therapy |
Volume | 11 |
DOIs | |
State | Published - 2018 |
Bibliographical note
Publisher Copyright:© 2018 Stenehjem et al.
Keywords
- Bladder cancer
- Checkpoint inhibitors
- Immunotherapy
- Pembrolizumab
- Tumor-mutation burden
- Urothelial cancer