Urothelial carcinoma therapy is a rapidly evolving and expanding field. Traditional cytotoxic chemotherapy regimens have not produced optimal long-term outcomes, and many urothelial cancer patients have comorbidities that disqualify them as chemotherapy candidates. In recent years, a plethora of novel therapeutic agents that target diverse molecular pathways has emerged as alternative treatment modalities for not only metastatic urothelial carcinoma, but also for muscle-invasive bladder cancer and non-muscle invasive bladder cancer in adjuvant and definitive settings. This review paper aims to discuss the various categories of therapeutic agents for these different types of urothelial cancer, discussing immunotherapy, antibody-drug conjugates, kinase inhibitors, CAR-T cell therapy, peptide vaccination, and other drugs targeting pathways such as angiogenesis, DNA synthesis, mTOR/PI3K/AKT, and EGFR/HER-2.
e14583 Background: Studies have suggested that concurrent corticosteroid use may decrease the efficacy of immunotherapy for cancer treatment, however, the data remains limited. The purpose of this study is to expand upon the previous literature to analyze the outcomes of patients with the following cancer sites: renal cell, lung, melanoma, urothelial, head and neck, hepatocellular, or breast cancer who received immunotherapy and steroids concurrently. Our primary objective was to analyze the overall survival (OS) and objective response rate (ORR) of patients receiving immunotherapy with corticosteroids compared to immunotherapy alone. Methods: A retrospective cohort study was conducted of patients receiving immunotherapy plus corticosteroids compared to immunotherapy alone using University of Texas Medical Branch patients. Patients receiving nivolumab, pembrolizumab, atezolizumab, ipilimumab, durvalumab, or avelumab between January 1, 2012-August 2020 with one of the following cancers were included in the analysis: Renal cell carcinoma, lung carcinoma, melanoma, urothelial carcinoma, head and neck carcinoma, hepatocellular carcinoma, and breast cancer carcinoma. The resulting sample was then separated into two arms. The experimental sample received any of the following steroids either as part of their therapeutic regimen or for symptom management and within 30 days of immunotherapy initiation or at any time during the immunotherapy regimen: dexamethasone, prednisone, methylprednisolone, or hydrocortisone. The control did not receive steroids within 30 days of initiation or during the course of their immunotherapy regimen. Weibull regression models were then constructed to compute hazard ratios for OS at 6 months, 12 months, and 3 years. ORR - complete and partial response, stable disease, and disease progression - between the two arms was assessed using a chi-squared test. Results: Two hundred and sixty patients met inclusion criteria. Of this, 164 received corticosteroids. Our sample was primarily male (70.38%), white (66.54%), and had 0-1 comorbidities (83.08%), lung cancer (45%), and metastases (81.92%). There was no significant difference between the two arms regarding sex, age, number of comorbidities, ECOG score, cancer type, or race. There was no statistically significant difference in OS between the experimental and control arm at 6 months (HR: 1.01; 95%CI 0.63-1.62), 12 months (1.02; 95% CI 0.69-1.51), or 3 years (1.06; 95% CI 0.79-1.42). There was no significant difference in ORR at 6 months between the two arms (2 = 6.3, p=0.178). Conclusions: There was no statistically significant difference in OS or PFS between the two study arms. This study suggests that corticosteroid use does not affect immunotherapy efficacy as previous literature suggests. Larger studies are needed to assess the impact of corticosteroids on immunotherapy efficacy in patients with cancer.
This a preprint and has not been peer reviewed. Data may be preliminary.
Plasmablastic lymphoma (PBL) is a rare form of non-Hodgkin lymphoma that is highly aggressive and carries a poor prognosis. Although the standard chemotherapy choice for most diffuse large B-cell lymphomas (DLBCL) is R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone), subtypes of DLBCL such as PBL are less responsive to this treatment regimen. The preferred regimens for PBL include infusional EPOCH (etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin hydrochloride), HyperCVAD (cyclophosphamide, vincristine sulfate, doxorubicin hydrochloride, and dexamethasone), or CODOX-M/IVAC (cyclophosphamide, vincristine, doxorubicin, high‐dose methotrexate/ifosfamide, etoposide, and high‐dose cytarabine). Recent studies have begun to investigate the addition of other agents to these regimens to improve survival. This case report is about a patient with a history of advanced acquired immunodeficiency syndrome (AIDS) with a cluster of differentiation 4 (CD4) count <20 who had CD20 negative plasmablastic lymphoma and was successfully treated with the combination of bortezomib and dose-adjusted EPOCH (V-EPOCH) and intrathecal chemotherapy, achieving complete response with optimal tolerance. To our knowledge, this is the first case to demonstrate a complete response with V-EPOCH for PBL in advanced AIDS with CD4 <20. We aim to highlight the importance of standardizing effective chemotherapeutic approaches to this cancer entity and augment the effectiveness of V-EPOCH therapy in the literature review.
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