Host metabolic factors and prognosis in patients treated with immune checkpoint inhibitors for advanced malignancies.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e14162-e14162
Author(s):  
Federica Biello ◽  
Marco Audisio ◽  
Silvia Genestroni ◽  
Gloria Borra ◽  
Francesca D'Avanzo ◽  
...  
Keyword(s):  
Clinical Outcome ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Multivariable Analysis ◽  
Progression Free Survival ◽  
Fold Increase ◽  
Advanced Melanoma ◽  
Host Metabolism ◽  
Increase In Risk

e14162 Background: It is well established that an altered host metabolism has an impact on cancer outcome, possibly mediated by several mechanisms, including hyperglicaemia, hyperinsulinemia and presence of chronic inflammation. The aim of our analysis was to evaluate the correlation between host metabolism and clinical outcome in patients with advanced melanoma, kidney and non-small cell lung cancer (NSCLC), treated with immune checkpoint inhibitors (anti-CTLA4, anti PD1 and anti PDL1). Methods: The relationship between presence of type 2 diabetes mellitus (DMII) at baseline and outcome was assessed in 187 patients treated with immune checkpoint inhibitors in two cancer centers. Progression Free Survival (PFS) and Overall Survival (OS) were calculated by Kaplan-Meier estimation; multivariate Cox analysis was performed according to age, gender, BMI (normal < 25 kg/m2, overweight 25-30 kg/m2, obese > 30 kg/m2), type of cancer and line of treatment. Results: One-hundred-sixty-eight patients were available for our analysis. Twenty-eight patients (17%) were diabetic at baseline. Median age was 65 (range 25-80); 83 patients were males (49%); 82 (48%) had advanced melanoma, 83 (49%) NSCLC and 3 (3%) kidney cancer. One-hundred-two (60%) patients had BMI < 25, 51 (30%) were overweight and 16 (10%) were obese. The first line of treatment was immunotherapy in 83 (49%) patients. By univariable analysis median PFS was 4.2 months in non diabetics vs 6.4 in diabetics patients (HR 0.95; 95%CI 0.58-1.58); median OS was 6.17 and 9.1 months, respectively (HR 1.00; 95%CI 0.58-1.75). At multivariable analysis, taking into account DMII, BMI, sex, age, line of treatment and type of cancer, we found that BMI ≤25 was associated with a two fold increase in risk of progression (PD) or death (p = 0.005), whereas patients who received immunotherapy as second or subsequent line had a two fold increase in risk of PD or death (p = 0.003). Conclusions: The results of our analysis show that in patients with advanced cancer treated with immune checkpoint inhibitors, the presence of DMII does not adversely affect the clinical outcome. Conversely, lower BMI was associated with a significantly worse PFS and OS, independently from type of cancer, age and gender. As expected, patients who received immunotherapy in later lines of treatment had a significantly shorter survival.

scholarly journals Antibiotics are associated with decreased progression-free survival of advanced melanoma patients treated with immune checkpoint inhibitors

2019 ◽  
Vol 8 (4) ◽  
pp. e1568812 ◽  
Author(s):  
Arielle Elkrief ◽  
Layal El Raichani ◽  
Corentin Richard ◽  
Meriem Messaoudene ◽  
Wiam Belkaid ◽  
...  
Keyword(s):  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Progression Free Survival ◽  
Advanced Melanoma ◽  
Free Survival ◽  
Melanoma Patients

PD-L1 SNPs as biomarkers to define benefit in patients with advanced NSCLC treated with immune checkpoint inhibitors

2021 ◽  
pp. 030089162110149
Author(s):  
Roberta Minari ◽  
Francesco Bonatti ◽  
Giulia Mazzaschi ◽  
Alessandra Dodi ◽  
Francesco Facchinetti ◽  
...  
Keyword(s):  
Clinical Outcome ◽  
Immune Checkpoint ◽  
Clinical Benefit ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Progression Free Survival ◽  
Nucleotide Polymorphisms ◽  
Entire Cohort ◽  
Programmed Death ◽  
Programmed Death 1

Objective: To investigate the role of CTLA-4, PD-1 (programmed death-1), and PD-L1 (programmed death-ligand 1) single nucleotide polymorphisms (SNPs) in predicting clinical outcome of patients with advanced non-small cell lung cancer (NSCLC) treated with immune checkpoint inhibitors (ICIs). Methods: A total of 166 consecutive patients were included. We correlated SNPs with clinical benefit, progression-free survival, time to treatment failure, and overall survival and evaluated the incidence of SNPs in nonresponder and long clinical benefit groups. Results: Considering the entire cohort, no correlation was found between SNPs and clinical outcome; however, PD-L1 rs4143815 SNP and the long clinical benefit group showed a statistically significant association ( p = 0.02). The nonresponder cohort displayed distinctive PD-L1 haplotype ( p = 0.05). Conclusion: PD-L1 SNPs seem to be marginally involved in predicting clinical outcome of NSCLC treated with ICI, but further investigations are required.

The Relationship of Diabetes Mellitus to Efficacy of Immune Checkpoint Inhibitors in Patients with Advanced Non-Small Cell Lung Cancer

Oncology ◽  
2021 ◽  
pp. 1-7
Author(s):  
Oded Jacobi ◽  
Yosef Landman ◽  
Daniel Reinhorn ◽  
Oded Icht ◽  
Michal Sternschuss ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Proportional Hazards ◽  
Checkpoint Inhibitors ◽  
Negative Relationship ◽  
Progression Free Survival ◽  
Significant Negative Correlation ◽  
Cox Proportional Hazards ◽  
Diabetic Patients

<b><i>Introduction:</i></b> Immune checkpoint inhibitors (ICI) are the new standard therapy in patients with metastatic NSCLC (mNSCLC). Metformin, previously associated with improved chemotherapy efficacy in diabetic and nondiabetic cancer patients, was recently associated with increased ICI efficacy. In this study, we aimed to explore the correlations between diabetes mellitus (DM), metformin use, and benefit from ICI in mNSCLC patients. <b><i>Methods:</i></b> All mNSCLC patients treated with ICI in our center between February 2015 and April 2018 were identified. Demographic and clinical data were extracted retrospectively. Cox proportional hazards regression, <i>t</i> tests, and χ<sup>2</sup> tests were employed to evaluate associations of progression-free survival (PFS), overall survival (OS), overall response rate (ORR), and disease control rate (DCR), with DM status, metformin use, and HbA1c levels, as appropriate. <b><i>Results:</i></b> Of 249 mNSCLC patients treated with ICI, 57 (22.8%) had DM. Thirty-seven (64.9% of all diabetic patients) patients were treated with metformin. A significant negative correlation of DM with PFS and OS was demonstrated (HR 1.5 [1.01–2.06], <i>p</i> = 0.011, and HR 1.5 [1.08–2.08], <i>p</i> = 0.017, respectively). Metformin exposure had no significant correlation with PFS or OS in diabetic mNSCLC patients (HR 1.08 [0.61–1.93], <i>p</i> = 0.79, and HR 1.29 [0.69–2.39], <i>p</i> = 0.42, respectively). There were no differences between groups with respect to ORR and DCR. <b><i>Conclusion:</i></b> Our data show a potential negative relationship between DM and ICI efficacy in mNSCLC patients. In contrast to reports with chemotherapy, we found no positive relationship between metformin use and ICI therapy in diabetic patients with mNSCLC. Further studies are needed to evaluate the effect of metformin in nondiabetic mNSCLC patients.

TERT promoter mutation as a prognostic marker in patients with advanced urothelial carcinoma treated with immune checkpoint inhibitors.

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 476-476
Author(s):  
Ivan de Kouchkovsky ◽  
Li Zhang ◽  
Errol Philip ◽  
Francis Wright ◽  
Daniel Myung Kim ◽  
...  
Keyword(s):  
Urothelial Carcinoma ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Univariate Analysis ◽  
Multivariable Analysis ◽  
Genomic Profiling ◽  
Clinical Variables ◽  
Tert Promoter ◽  
Visceral Metastases

476 Background: Reliable predictive markers are lacking in patients (pts) with locally advanced or metastatic urothelial carcinoma (aUC) treated with immune checkpoint inhibitors (ICI). We sought to determine whether specific genomic alterations could be used to predict overall survival (OS) in this patient population. Methods: We undertook a retrospective cohort study of pts with aUC who received ICI and underwent genomic profiling by next-generation sequencing (NGS). All patients underwent NGS using commercially available platforms (e.g. Foundation Medicine, Strata, Invitae), or testing on the CLIA-certified institutional panel UCSF500. Associations between the 20 most frequently altered genes and OS were first examined by Cox regression. Genes with a p <0.1 on univariate analysis and relevant clinical variables were then included in a multivariable analysis. Results: We identified 78 pts treated with ICI for aUC with available genomic profiling results. Median age at ICI initiation was 71; the majority of patients had visceral metastases (70.5%), ECOG performance status ≤1 (62.8%) and received ICI in the post-platinum setting (52.6%). Objective response rate in this cohort was 35.9%, median progression free survival was 4.0 months (95% CI 2.6-10.5) and median OS was 17.5 months (95% CI 14.1-NR) from ICI start. The most commonly altered genes were the TERT promoter (TERTp) (61%), TP53 (52%), RB1 (31%), CDKN2A(29%) and CDKN2B (27%). On univariable analysis there was a trend towards longer OS in pts with TERTp mutations (HR 0.53, 95% CI 0.27-1.06, p = 0.07), and shorter OS in pts with CDKN2B mutations (HR 1.91, 95% CI 0.98-3.73, p = 0.06). Both mutations were included in a multivariable analysis. After adjusting for known prognostic variables (ECOG PS, visceral metastases, albumin, hemoglobin, body mass index [BMI], neutrophil to lymphocyte ratio [NLR], and histology), the presence of a TERTp mutation was significantly associated with improved OS (HR 0.30, 95% CI 0.10-0.93, p = 0.04; Table). Conclusions: The presence of a TERTp mutation was an independent predictor of improved OS in a cohort of aUC pts treated with ICI. Other common mutations and clinical variables were not associated with OS on a multivariable analysis. These findings are hypothesis-generating and prospective validation is needed. [Table: see text]

The association between albumin-globulin ratio (AGR) and survival in patients treated with immune checkpoint inhibitors

2021 ◽  
pp. 1-11
Author(s):  
Deniz Can Guven ◽  
Oktay Halit Aktepe ◽  
Melek Seren Aksun ◽  
Taha Koray Sahin ◽  
Gozde Kavgaci ◽  
...  
Keyword(s):  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Multivariate Analyses ◽  
Checkpoint Inhibitors ◽  
Progression Free Survival ◽  
Free Survival ◽  
Patients With Cancer ◽  
Early Progression ◽  
Term Benefit

BACKGROUND: The albumin-globulin ratio (AGR) could be a prognostic biomarker in patients with cancer, although the data is limited in patients treated with immune-checkpoint inhibitors (ICIs). OBJECTIVES: We aimed to evaluate the association between AGR and survival in ICI-treated patients. METHODS: The data of 212 advanced-stage patients were retrospectively evaluated in this cohort study. The association between AGR with overall (OS) and progression-free survival (PFS) were evaluated with multivariate analyses. Additionally, receptor operating curve (ROC) analysis was conducted to assess the AGR’s predictive power in the very early progression (progression within two months) and long-term benefit (more than twelve months survival). RESULTS: The median AGR was calculated as 1.21, and patients were classified into AGR-low and high subgroups according to the median. In the multivariate analyses, patients with lower AGR (< 1.21) had decreased OS (HR: 1.530, 95% CI: 1.100–2.127, p= 0.011) and PFS (HR: 1.390, 95% CI: 1.020–1.895, p= 0.037). The area under curve of AGR to detect early progression and long-term benefit were 0.654 (95% CI: 0.562–0.747, p= 0.001) and 0.671 (95% CI: 0.598–0.744, p< 0.001), respectively. CONCLUSIONS: In our experience, survival with ICIs was impaired in patients with lower AGR. Additionally, the AGR values could detect the very early progression and long-term benefit ICIs.

Immune-checkpoint inhibitors versus other systemic therapies in advanced head and neck cancer: a network meta-analysis

Immunotherapy ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 541-555
Author(s):  
Lingrong Tang ◽  
Tingting Liu ◽  
Jun Chen ◽  
Jun Dang ◽  
Guang Li
Keyword(s):  
Head And Neck Cancer ◽  
Head And Neck ◽  
Neck Cancer ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Meta Analysis ◽  
Objective Response ◽  
Progression Free Survival ◽  
Systemic Therapies

Aim: We assessed the efficiency of immune checkpoint inhibitors relative to other systemic therapies in previously treated recurrent/metastatic head and neck cancer. Materials & methods: Relative treatment effects were assessed from eligible randomized controlled trials using Bayesian network meta-analyses. Results: Among 15 trials evaluating 14 treatments, nivolumab achieved the best overall survival (OS) benefit; zalutumumab and buparlisib + paclitaxel provided the best progression-free survival benefit and objective response rate. Buparlisib + paclitaxel and zalutumumab were associated with the best OS rate at 6 and 12 months, respectively; nivolumab yielded the best OS rate at 18–24 months. Conclusion: Nivolumab was the most favorable treatment. Zalutumumab and buparlisib + paclitaxel had better efficiency, and might be a better selection for patients with programmed death-ligand 1-low/negative tumors than other treatments.

Abstract 15395: Immune Checkpoint Inhibitors for Cancer Are Associated With Increased Venous Thromboembolism Events

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Jingyi Gong ◽  
Zsofia Drobni ◽  
Raza Alvi ◽  
Sean Murphy ◽  
Sarah Hartmann ◽  
...  
Keyword(s):  
Venous Thromboembolism ◽  
Immune Activation ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Massachusetts General Hospital ◽  
Control Period ◽  
Fold Increase ◽  
Vein Thrombosis ◽  
Increased Risk

Introduction: Immune checkpoint inhibitors (ICI) lead to immune activation, increased inflammation and cancer cell death. Both immune activation and inflammation are critical pathobiological drivers for venous thromboembolism (VTE). There are no robust data testing the effect of ICIs on the risk of developing VTE. Methods: This is a retrospective study of 2854 patients who received ICIs at Massachusetts General Hospital, Boston, MA. VTE events, defined as a composite of deep vein thrombosis (DVT) or pulmonary embolism (PE), were identified by individual chart review and were blindly adjudicated using standard criteria. A case-crossover design was applied with an “at-risk period” defined as the two-year period after and the “control period” as the two years prior to treatment. Incidence rate ratio (IRR) was calculated using Poisson’s regression. Results: Immune checkpoint inhibitor use increased VTE risk by 1.84-fold from 4.85 per 100-person years to 8.91 per 100 person-years (IRR 1.84, 95% confidence interval: 1.54 - 2.19, p <0.001). Of the individual components, there was a 2.44-fold increase in DVT risk (2.30 to 5.58 per 100 person-years) and 1.68-fold increase in PE risk (2.96 to 5.00 per 100 person-years). Comparing patients with and without a VTE event, those with a VTE event after ICI initiation had a higher rate of prior VTE, lung cancer, urothelial cancer, and a higher platelet count and white blood cell count at baseline. At 6 months post ICI initiation, 165 (8.6%) patients had a VTE event and of these patients 136 (7.1%) had no prior VTE. Conclusions: Patients with cancer treated with ICIs are at increased risk of developing VTE. Whether prophylaxis for VTE among patients starting an ICI reduces this risk is unclear.

Comparative Analysis of Durable Responses on Immune Checkpoint Inhibitors Versus Other Systemic Therapies: A Pooled Analysis of Phase III Trials

2019 ◽  
pp. 1-10 ◽  
Author(s):  
Elvire Pons-Tostivint ◽  
Aurélien Latouche ◽  
Pauline Vaflard ◽  
Francesco Ricci ◽  
Delphine Loirat ◽  
...  
Keyword(s):  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Durable Response ◽  
Free Survival ◽  
Drug Classes ◽  
Metastatic Setting ◽  
The Mean

PURPOSE Immune checkpoint inhibitors (ICIs) have been demonstrated to improve overall survival (OS) in several tumor types. Durable responses have been reported with these agents in patients with melanoma and lung cancer. We aimed to quantify the proportion of patients who experience durable responses on ICIs and to compare it with other drug classes. PATIENTS AND METHODS We retrieved published phase III randomized trials that included at least one ICI arm in the recurrent and/or metastatic setting. A durable response to treatment was defined as a progression-free survival that exceeded three times the median progression-free survival of the whole population. The proportion of patients who experienced an OS that exceeded two times the median OS of the whole patient population also was estimated. RESULTS Nineteen studies involving 11,640 patients treated in 42 treatment arms (26 ICI and 16 non-ICI arms) were included. The mean proportion of patients who experienced a durable response was 2.3 times higher in those treated with an ICI compared with those treated in the control arms (25% v 11%). Durable responses were more frequent in patients treated with anti–PD-1/PD-L1 agents than in patients treated with anti–CTLA-4 agents (28% v 18%). The mean proportion of patients who had an OS that exceeded two times the median OS was also higher in those treated with ICIs than in those treated in the control arms (30% v 23%). In multivariable analysis, the effects of treatment with anti–PD-1/PD-L1 agents and of first-line treatment were statistically associated with a higher mean proportion of durable responses. CONCLUSION Durable responses were more frequent in patients treated with ICIs, although they also occurred in patients treated with other drug classes.

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