Browsing by Subject "PD-1"
Now showing 1 - 3 of 3
Results Per Page
Sort Options
Item Open Access First-line treatment of metastatic melanoma: role of nivolumab.(Immunotargets Ther, 2017) Force, Jeremy; Salama, April KsHistorically, the median overall survival of metastatic melanoma patients was less than 1 year and long-term survivors were rare. Recent advances in therapies have dramatically shifted this landscape with increased survival rates and the real possibility that long-term disease control is achievable. Advances in immune modulators, including cytotoxic T-lymphocyte antigen-4 and programmed death-1 based treatments, have been an integral part of this success. In this article, we review previous and recent therapeutic developments for metastatic melanoma patients. We discuss advances in immunotherapy while focusing on the use of nivolumab alone and in combination with other agents, including ipilimumab in advanced melanoma. One major goal in melanoma research is to optimize combination strategies allowing for more patients to experience benefit while minimizing toxicity. A better understanding of the optimal sequencing, combinations, and mechanisms underlying the development of resistance may provide evidence for rational clinical trial designs of novel immunotherapy strategies in melanoma and other cancer subtypes.Item Open Access Mechanisms of immune-related adverse events during the treatment of cancer with immune checkpoint inhibitors.(Rheumatology (Oxford, England), 2019-12) Weinmann, Sophia C; Pisetsky, David SImmune checkpoint inhibitors are novel biologic agents to treat cancer by inhibiting the regulatory interactions that limit T cell cytotoxicity to tumours. Current agents target either CTLA-4 or the PD-1/PD-L1 axis. Because checkpoints may also regulate autoreactivity, immune checkpoint inhibitor therapy is complicated by side effects known as immune-related adverse events (irAEs). The aim of this article is to review the mechanisms of these events. irAEs can involve different tissues and include arthritis and other rheumatic manifestations. The frequency of irAEs is related to the checkpoint inhibited, with the combination of agents more toxic. Because of their severity, irAEs can limit therapy and require immunosuppressive treatment. The mechanisms leading to irAEs are likely similar to those promoting anti-tumour responses and involve expansion of the T cell repertoire; furthermore, immune checkpoint inhibitors can affect B cell responses and induce autoantibody production. Better understanding of the mechanisms of irAEs will be important to improve patient outcome as well as quality of life during treatment.Item Open Access PD-L1/PD-1 Biomarker for Metastatic Urothelial Cancer that Progress Post-platinum Therapy: A Systematic Review and Meta-analysis.(Bladder cancer (Amsterdam, Netherlands), 2019-11-22) Tan, Wei Phin; Tan, Wei Shen; Inman, Brant ABackground
Immune checkpoint inhibitors (ICI) are extremely expensive and most patients with metastatic urothelial carcinoma (mUC) do not benefit significantly from their use.Objective
We performed a systematic review and meta-analysis to determine response rates and survival outcomes on patients with mUC progressing despite prior platinum-based chemotherapy receiving ICI stratified by biomarker status.Methods
We performed a comprehensive literature search for all articles in PubMed and Embase up to 06/15/2019 to identify all studies pertaining to programmed death-ligand 1 (PD-L1) and programmed death 1 (PD-1) receptor targeted therapies for mUC that reported biomarkers. Given that biomarkers are reported on different scales and with different metrics, we defined each biomarker as either positive or negative using the definitions implemented in each individual trial. We meta-analyzed the data, reconstructed overall (OS) and progression-free survival (PFS) curves, and analyzed response rates by biomarker status. OS and PFS were analyzed in a pooled Kaplan-Meier analysis and pseudo-individualized patient data (IPD) extracted.Results
We identified 1429 manuscripts of which 8 met inclusion criteria, with a total of 1837 treated patients with outcomes data. On proportional hazards survival analysis, patients in the biomarker negative group were associated with a lower PFS (HR 1.48, 95% CI: 1.18 - 1.85, p < 0.001) and lower OS (HR 1.54, 95% CI: 1.32 - 1.80, p < 0.001) when compared to the biomarker positive group. Response data was available for 1641 patients and random effects proportion show complete response in 8% and 3% in biomarker positive and negative patients, respectively.Conclusions
ICI therapy for metastatic UC post platinum therapy has a higher overall response rate, OS and PFS in patients who are biomarker positive compared to those who are negative. However, some patients who are biomarker negative do achieve complete responses. A better biomarker for patient selection is essential before biomarkers can be used to stratify candidates for ICI therapy.