Characterization of outcomes in patients with advanced genitourinary malignancies treated with immune checkpoint inhibitors.
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SUBMITTER: Ma VT
PROVIDER: S-EPMC8286282 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Although immune-mediated therapies have been used in genitourinary (gu) malignancies for decades, recent advances with monoclonal antibody checkpoint inhibitors (cpis) have led to a number of promising treatment options. In renal cell carcinoma (rcc), cpis have been shown to have benefit over conventional therapies in a number of settings, and they are the standard of care for many patients with metastatic disease. Based on recent data, combinations of cpis and antiangiogenic therapies are likely to become a new standard approach in rcc. In urothelial carcinoma, cpis have been shown to have a role in the second-line treatment of metastatic disease, and a number of clinical trials are actively investigating cpis for other indications. In other gu malignancies, such as prostate cancer, results to date have been less promising. Immunotherapies continue to be an area of active study for all gu disease sites, with several clinical trials ongoing. In this review, we summarize the current evidence for cpi use in rcc, urothelial carcinoma, prostate cancer, testicular germ-cell tumours, and penile carcinoma. Ongoing clinical trials of interest are highlighted, as are the challenges that clinicians and patients will potentially face as immune cpis become a prominent feature in the treatment of gu cancers.
| S-EPMC7194001 | biostudies-literature
Project description:BackgroundReal-world data enables evaluation of immune checkpoint inhibitor (ICI) use in advanced melanoma management. We examined characteristics and outcomes of ICI-treated patients with advanced melanoma and organ dysfunction (baseline and emergent).Materials and methodsThis retrospective observational study used electronic health records derived from a nationwide data set to examine advanced melanoma patients treated with first-line ICIs (2011-2018). Clinical characteristics, real-world time to treatment discontinuation (rwTTD), and overall survival (OS) were analyzed for patients with normal organ function and those with organ dysfunction prior to ICI initiation. Patients with emergent dysfunction in the 90 days following ICI initiation were identified, and potentially associated characteristics were explored.ResultsOf 2,407 patients included, 1,884 and 1,717 had evaluable renal and hepatic laboratory values, respectively. Patients with baseline renal dysfunction (2.4%) were older and more frequently male, and less frequently treated with ICI combinations, than patients with normal renal function. Patients with baseline hepatic dysfunction (2.8%) were similar to patients with normal hepatic function regarding demographics and treatments received. Patients with baseline organ dysfunction displayed shorter rwTTD and OS. Among patients with normal baseline organ function, 4.6% and 7.4% developed renal and hepatic dysfunction within 90 days of ICI initiation, respectively; this was associated with combination ICI treatment.ConclusionPatients with advanced melanoma and baseline organ dysfunction frequently receive ICI treatment but have poorer clinical outcomes than patients with normal organ function. Among patients with normal renal and hepatic function at ICI initiation, emergent organ dysfunction rates in this real-world cohort are similar to those reported in clinical trials.Implications for practiceReal-world data provide an opportunity to understand treatment patterns, toxicity, and clinical outcomes among patients treated outside of clinical trials. This study confirms that patients with advanced melanoma and baseline renal or hepatic dysfunction are being treated with ICI therapy more frequently as monotherapy than in combination therapy. For those real-world patients with normal baseline organ function, emergent renal and hepatic dysfunction are both more common in patients treated with combination versus ICI monotherapy.
| S-EPMC7648349 | biostudies-literature
Project description:In the present study, the influence of purely palliative radiotherapy (pRT) on the outcomes of patients with advanced cancer undergoing immune checkpoint blockade was evaluated. Patients were stratified into three groups: Patients who had received pRT within 6 months prior to the initiation of immunotherapy (previous pRT); patients who received pRT during immunotherapy (concurrent pRT); and patients who did not receive RT prior to or during immunotherapy (no RT group), and these groups were compared. The median overall survival (mOS), median progression free survival (mPFS) and median time-to-treatment failure (mTTF) for the previous pRT group were significantly shorter compared with the no RT group (mOS, 3.6 vs. 12.1 months, respectively, P=0.0095; mPFS 1.8 vs. 5.4 months, respectively, P=0.0016; mTTF 1.8 vs. 5.7 months, respectively, P=0.0035). The concurrent pRT group had a longer mTTF compared with the previous pRT group and similar outcomes to the no RT group. In the previous pRT group, 26.9% of the patients experienced immune-related adverse events compared with 40.1% of patients in the no RT group. Despite the use of pRT during immunotherapy being considered safe, the results of the present study suggest that pRT has a negative effect on immune balance.
| S-EPMC6951237 | biostudies-literature
Project description:Gastrointestinal (GIT) tumors are extremely fatal and lethal tumors with limited therapeutic options. Antitumor immunity is new line of research in management of solid tumors. Immune check points are negative regulators of immune system and control the immune response. These checkpoints are exploited by cancer cells. Cancer cells causes early activation of checkpoints and suppress the immune response, and therefore have unchecked growth and metastasis of malignant cells. Immune checkpoint inhibitors (ICIs), downregulates these checkpoints and activate the proliferation of cytotoxic T cells which helps in lysis of tumor cells. ICIs have shown the promising results in management of melanoma, non-small cell lung cancer and renal cell carcinoma. Encouraged by their recent success in solid tumors many clinical trials are ongoing to evaluate their efficacy in GIT tumors. In this article we will try to explain rationale for use of ICIs in GIT tumors. We will summarize the ongoing research, preliminary results and future aspects of ICIs in GIT malignancies.
| S-EPMC5934142 | biostudies-literature
Project description:BACKGROUND:Myocarditis is an uncommon, but potentially fatal, toxicity of immune checkpoint inhibitors (ICI). Myocarditis after ICI has not been well characterized. OBJECTIVES:The authors sought to understand the presentation and clinical course of ICI-associated myocarditis. METHODS:After observation of sporadic ICI-associated myocarditis cases, the authors created a multicenter registry with 8 sites. From November 2013 to July 2017, there were 35 patients with ICI-associated myocarditis, who were compared to a random sample of 105 ICI-treated patients without myocarditis. Covariates of interest were extracted from medical records including the occurrence of major adverse cardiac events (MACE), defined as the composite of cardiovascular death, cardiogenic shock, cardiac arrest, and hemodynamically significant complete heart block. RESULTS:The prevalence of myocarditis was 1.14% with a median time of onset of 34 days after starting ICI (interquartile range: 21 to 75 days). Cases were 65 ± 13 years of age, 29% were female, and 54% had no other immune-related side effects. Relative to controls, combination ICI (34% vs. 2%; p < 0.001) and diabetes (34% vs. 13%; p = 0.01) were more common in cases. Over 102 days (interquartile range: 62 to 214 days) of median follow-up, 16 (46%) developed MACE; 38% of MACE occurred with normal ejection fraction. There was a 4-fold increased risk of MACE with troponin T of ?1.5 ng/ml (hazard ratio: 4.0; 95% confidence interval: 1.5 to 10.9; p = 0.003). Steroids were administered in 89%, and lower steroids doses were associated with higher residual troponin and higher MACE rates. CONCLUSIONS:Myocarditis after ICI therapy may be more common than appreciated, occurs early after starting treatment, has a malignant course, and responds to higher steroid doses.
| S-EPMC6196725 | biostudies-literature
Project description:As the incidence of cutaneous malignancies continues to rise and their treatment with immunotherapy expands, dermatologists and their patients are more likely to encounter immune checkpoint inhibitors. While the blockade of immune checkpoint target proteins (cytotoxic T-lymphocyte-associated protein-4, programmed cell death-1, and programmed cell death ligand-1) generates an antitumor response in a substantial fraction of patients, there is a critical need for reliable predictive biomarkers and approaches to address refractory disease. The first article of this Continuing Medical Education series reviews the indications, efficacy, safety profile, and evidence supporting checkpoint inhibition as therapeutics for metastatic melanoma, cutaneous squamous cell carcinoma, and Merkel cell carcinoma. Pivotal studies resulting in the approval of ipilimumab, pembrolizumab, nivolumab, cemiplimab, and avelumab by regulatory agencies for various cutaneous malignancies, as well as ongoing clinical research trials, are discussed.
| S-EPMC7572574 | biostudies-literature
Project description:BackgroundThe effect of sarcopenia on the clinical outcomes of patients with malignant neoplasms receiving immune checkpoint inhibitors (ICIs) is unclear. The aim of this study was to evaluate the effect and survival of patients with malignancies and sarcopenia receiving ICIs.MethodsWe systematically searched related studies in PubMed, Embase, and Cochrane Library up to March 2021 according to the inclusion and exclusion criteria. Information pertaining to the hazard ratio (HR) corresponding to 95% confidence interval (CI) of overall survival (OS) and progression-free survival (PFS) as determined by univariate and multivariate analyses; the odds ratio (OR) corresponding to the 95% CI of the disease control rate (DCR) and objective response rate (ORR); and immune-related adverse events (irAEs) was collected and analyzed using the RevMan 5.4 software. Study heterogeneity and sensitivity were also assessed.ResultsA total of 19 studies were finalized that included 1763patients with lung, gastrointestinal, and head and neck cancers as well as those with melanoma, renal cell carcinoma, urothelial carcinoma, pancreatic cancer, and soft tissue sarcoma. According to univariate and multivariate analyses, patients with sarcopenia at pre-immunotherapy had poorer PFS and OS than those without. HRs and the corresponding 95% CI of PFS were 1.91(1.55-2.34, p <0.00001) and 1.46 (1.20-1.78, p =0.0001), respectively, and HRs and the corresponding 95% CI of OS were 1.78 (1.47-2.14, p <0.00001) and 1.73 (1.36-2.19, p <0.0001), respectively. Patients with sarcopenia showed poor PFS and OS during treatment. In addition, patients with sarcopenia had worse ORR (OR 0.46, 95% CI 0.28-0.74, p = 0.001) and DCR (OR 0.44, 95% CI 0.31-0.64, p<0.0001); however, the incidence of irAEs of any grade and high-grade in patients with sarcopenia did not increase, OR and the corresponding 95% CI were 0.58(0.30-1.12, p = 0.10) and 0.46(0.19-1.09, p = 0.08). Further, we performed subgroup analysis, skeletal muscle mass index (SMI) and psoas muscle mass index (PMI) stratification. In the SMI group, patients with sarcopenia had poor ORR, DCR, PFS, and OS than those without. In the PMI group, sarcopenia had poor ORR,DCR, and was a poor prognostic factor for PFS and OS according to univariate analysis but had no effect on PFS and OS according to multivariate analysis.ConclusionsPatients with malignancies and sarcopenia at pre-immunotherapy or follow-up visits had poorer clinical outcomes than those without, and sarcopenia was a poor predictive factor of ICI immunotherapy outcomes.
| S-EPMC8427761 | biostudies-literature
Project description:IntroductionHyperprogressive disease (HPD) is a paradoxically rapid disease progression during or shortly after antitumor treatment, especially immune checkpoint inhibitors (ICIs). Various diagnosis criteria of HPD cause heterogeneous incidence rates in different clinical research, and there is no consensus on potential risk factors associated with HPD occurrence. Hence, we aimed to summarize incidence of HPD in ICI treatment for solid tumors. Clinicopathological factors associated with HPD are also analyzed.MethodsClinical studies about HPD during/after ICI treatment of solid malignancies are included. Pubmed, Embase, and Cochrane library were searched for eligible studies published before October 7. The Newcastle-Ottawa scale was used to assess the quality of the included studies. Random effect and fixed effect models were, respectively, used for pooling incidence of HPD and analysis of risk factors for HPD. Heterogeneity, subgroup analysis, and publication bias were also analyzed. All meta-analysis was performed via R software (y -40v4.0.2).ResultsForty-one studies with 6009 patients were included. The pooled incidence of HPD was 13.2% (95% CI, 11.2%-15.4%). Head and neck cancer (HNC) had the highest incidence of HPD (18.06%), and melanoma had the lowest (9.9%). Tumor types (P = .0248) and gender ratio (P = .0116) are sources of heterogeneity of pooled incidence of HPD. For five clinicopathological factors associated with HPD, only programmed cell death protein 1 ligand 1 (PD-L1) positivity was a preventive factor (odds ratio = 0.61, P <.05). High lactate dehydrogenase (LDH) level (OR = 1.51, P = .01), metastatic sites >2 (OR = 2.38, P <.0001), Eastern Cooperative Oncology Group Performance Score ≥2 (OR = 1.47, P = .02), and liver metastasis (OR = 3.06, P <.0001) indicate higher risk of HPD.ConclusionsThe pooled incidence of HPD was less than 15%, and HNC had the highest incidence of HPD. LDH and PD-L1 are remarkable biomarkers for prediction of HPD in future medical practice.
| S-EPMC9381837 | biostudies-literature
Project description:Immune checkpoint inhibitors (ICI) have revolutionized the treatment landscape of several solid tumor types. However, as patient outcomes are heterogeneous, clinical tools to aid in prognostication are needed. The Lung Immune Prognostic Index (LIPI) correlates with outcomes in patients with non-small cell lung cancer (NSCLC) treated with ICI, but its applicability beyond NSCLC is poorly defined. We sought to determine whether LIPI is associated with overall survival (OS), progression-free survival (PFS) and objective response rate (ORR) in a pooled, real-world, retrospective cohort of patients with solid tumors treated with ICI. Of the total pooled cohort (N = 578), 47.2%, 38.2% and 14.5% of patients were stratified into good, intermediate and poor LIPI group, respectively. Median OS were 22.8 (95% CI 17.4-29.5), 7.8 (95% CI 6.6-9.6), and 2.5 months (95% CI 1.4-3.4) (p < 0.0001). Median PFS were 9.9 (95% CI 7.2-11.5), 3.6 (95% CI 2.7-4.3), and 1.4 months (95% CI 1.2-2.2) (p < 0.0001). ORR was also associated with LIPI group (p < 0.001). Intermediate and poor LIPI were independently prognostic of OS compared to good LIPI, with hazard ratios (HR) of 1.8 (95% CI 1.4-2.3, p < 0.001) and 3.6 (95% CI 2.5-5.1, p < 0.001), respectively. These data are the first to suggest that in a real-world setting, the prognostic value of LIPI may be tumor agnostic.
| S-EPMC6896022 | biostudies-literature
Project description:Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of several solid and hematological malignancies. ICIs are not only able to produce long and durable responses, but also very well tolerated by patients. There are several approved indications of use of ICIs in treatment of metastatic gastrointestinal malignancies including gastric, esophageal, colorectal and hepatocellular carcinoma. In addition, ICIs can be used in microsatellite instability-high (MSI-H) and high tumor mutational burden (TMB) tumors in chemotherapy-resistant setting. Despite having good efficacy and superior safety profile, ICIs are clinically active in small subset of patients, therefore, there is a huge unmet need to enhance their efficacy and discover new predictive biomarkers. There are several ongoing clinical trials that are exploring the role of ICIs in various gastrointestinal cancers either as single agent or in combination with chemotherapy, radiation therapy, targeted agents or other immunotherapeutic agents. In this review, we discuss the published and ongoing trials for ICIs in gastrointestinal malignancies, including esophageal, gastric cancer, pancreatic, hepatocellular, biliary tract, colorectal and anal cancers. Specifically, we focus on the use of ICIs in each line of therapy and discuss the future directions of these agents in each type of gastrointestinal cancer.
| S-EPMC7463795 | biostudies-literature