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.

scholarly journals CMET-12. EFFICACY OF UPFRONT IMMUNE CHECKPOINT INHIBITORS IN LUNG CANCER BRAIN METASTASIS

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi53-vi53
Author(s):  
Addison Barnett ◽  
Adam Lauko ◽  
Hong Li ◽  
Assad Ali ◽  
Soumya Sagar ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Brain Metastasis ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Proportional Hazards ◽  
Checkpoint Inhibitors ◽  
Tertiary Care ◽  
Cox Proportional Hazards ◽  
Rank Test ◽  
Cox Proportional Hazards Models

Abstract INTRO/OBJECTIVE Immune checkpoint inhibitors (ICI) have improved outcomes in a subset of patients with lung cancer. However, data describing the efficacy of ICI in lung cancer brain metastasis (LCBM) is limited. We analyzed overall survival (OS) in patients with LCBM treated with upfront ICI, defined as having received ICI within 90-days of LCBM diagnosis, compared to non-ICI therapies. METHODS We reviewed 665 patients with LCBM diagnosed between 2000 and 2018 at a major tertiary care institution. Of those patients, 240 received ICI, 164 of which received ICI after 90-days and 76 received ICI within 90-days. Propensity score (PS) was calculated by logistic regression model including age, KPS, number of baseline brain lesions, and presence of extra-cranial metastasis (ECM) at time of LCBM diagnosis. OS from LCBM diagnosis between PS matched cohorts were compared using Kaplan-Meier, the Log-Rank test, and Cox proportional hazards models. RESULTS Prior to PS matching, median survival between ICI and non-ICI cohorts was not significantly different (10.9 months for both, p=0.81), although more ICI patients had ECM (57.1% vs 40.9%, p=0.006). Following PS matching, the ICI (n=76) and non-ICI (n=76) cohorts had median age (62.4 vs 62.3 years), KPS (80 for both), lesion number (2 for both), and ECM (56.6% for both). Of matched patients, 94% received SRS, 52% received WBRT, and 29% underwent surgical resection. Compared to non-ICI, the ICI cohort had a 2-year OS hazard ratio=0.87 (95% CI=0.58–1.31, p=0.51). Median and 1-year survival were not significantly different between ICI and non-ICI cohorts (median: 10.9 vs 9.1 months; 1-yr: 43.0% vs 42.4%). CONCLUSION Patients with LCBM who received ICI within 90-days of their diagnosis did not have improvement in OS compared to patients who received non-ICI therapies. Evaluation of clinical factors that may affect the efficacy and durability of immunotherapy is ongoing and will be presented.

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.

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.

scholarly journals Immunotherapy in Hepatocellular Carcinoma: Is There a Light at the End of the Tunnel?

Cancers ◽  
2019 ◽  
Vol 11 (8) ◽  
pp. 1078 ◽  
Author(s):  
Amit Mahipal ◽  
Sri Harsha Tella ◽  
Anuhya Kommalapati ◽  
Alexander Lim ◽  
Richard Kim
Keyword(s):  
Hepatocellular Carcinoma ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Primary Liver Cancer ◽  
Progression Free Survival ◽  
The United States ◽  
Hepatic Reserve ◽  
Dismal Prognosis ◽  
United States Food

Hepatocellular carcinoma (HCC) is the most common primary liver cancer with dismal prognosis when diagnosed at advanced stages. Surgical resection of the primary tumor or orthotropic liver transplantation serves as a potential curative option. However, this approach is highly dependent on the hepatic reserve and baseline functional status of the patient. Liver directed therapies such as portal vein embolization (PVE), trans-arterial chemoembolization (TACE), and systemic chemotherapy are employed in non-surgical candidates. Sorafenib was the only approved systemic therapeutic agent for almost a decade until the recent approval of lenvatinib by the United States Food and Drug Administration (FDA) as an alternate first-line agent. Regorafenib, nivolumab, pembrolizumab and cabozantinib are approved by the FDA as second-line agents in patients who failed or could not tolerate sorafenib. Ramucirumab was recently FDA approved for the subset of patients that have high alfa-fetoprotein levels (>400 ng/mL). A better understanding of tumorigenesis and encouraging clinical trial results that evaluated immune-checkpoint inhibitors opened doors for immunotherapy in HCC. Immune checkpoint inhibitors have demonstrated a prolonged median overall and progression-free survival in a subset of patients with HCC. On-going translational and clinical research will hopefully provide us with a better understanding of tumor markers, genetic aberrations and other factors that determine the immunotherapy response in HCC. In this review, we sought to summarize the potential role and future directions of immunotherapy in the management of HCC.

scholarly journals Salvage Ipilimumab and Nivolumab in Patients With Metastatic Renal Cell Carcinoma After Prior Immune Checkpoint Inhibitors

2020 ◽  
Vol 38 (27) ◽  
pp. 3088-3094 ◽  
Author(s):  
Anita Gul ◽  
Tyler F. Stewart ◽  
Charlene M. Mantia ◽  
Neil J. Shah ◽  
Emily Stern Gatof ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Targeted Therapy ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Response Rate ◽  
Checkpoint Inhibitors ◽  
Objective Response ◽  
Progression Free Survival ◽  
Free Survival ◽  
Metastatic Rcc

PURPOSE Immune checkpoint inhibitors (ICIs) are standard therapy in metastatic renal cell carcinoma (RCC). The safety and activity of the combination of ipilimumab and nivolumab in patients who have received prior ICI targeting the programmed death 1 (PD-1) pathway remains unknown. We evaluated ipilimumab and nivolumab in patients with metastatic RCC after prior treatment with anti–PD-1 pathway–targeted therapy. PATIENTS AND METHODS Patients with metastatic RCC who received prior anti–PD-1 pathway-targeted therapy and subsequently received ipilimumab and nivolumab were reviewed. Objective response rate and progression-free survival per investigator assessment were recorded. Toxicity of ipilimumab and nivolumab was also assessed. RESULTS Forty-five patients with metastatic RCC were included. All patients (100%) received prior ICIs targeting the PD-1 pathway. The median age was 62 years (range, 21-82 years). At a median follow-up of 12 months, the objective response rate to ipilimumab and nivolumab was 20%. The median progression-free survival while on ipilimumab and nivolumab was 4 months (range, 0.8-19 months). Immune-related adverse events (irAEs) of any grade with ipilimumab and nivolumab were recorded in 29 (64%) of the 45 patients; grade 3 irAEs were recorded in 6 (13%) of the 45 patients. CONCLUSION Ipilimumab and nivolumab demonstrated antitumor activity with acceptable toxicity in patients with metastatic RCC who had prior treatment with checkpoint inhibition.

scholarly journals Efficacy of immune checkpoint inhibitors and age in cancer patients

Immunotherapy ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 587-603 ◽  
Author(s):  
Xuan-zhang Huang ◽  
Peng Gao ◽  
Yong-xi Song ◽  
Jing-xu Sun ◽  
Xiao-wan Chen ◽  
...  
Keyword(s):  
Cancer Patients ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Progression Free Survival ◽  
Comparable Efficacy ◽  
Control Groups ◽  
Free Survival ◽  
Meta Regression Analysis ◽  
The Impact

Aim: To evaluate the impact of age on the efficacy of immune checkpoint inhibitors (ICI) in cancer patients. Materials & methods: The primary outcomes included overall survival (OS) and progression-free survival (PFS). Subgroup, meta-regression analysis and within-trial interaction HR were conducted. Results: A total of 34 studies containing 20,511 cancer patients were included. ICI could improve the OS and PFS in patient aged <65 and ≥65 years. Patients aged <75 years treated with ICI also had favorable OS and PFS compared with the control groups. Conclusion: ICI has comparable efficacy in cancer patients aged <65 and ≥65 years. Cancer patients aged ≥75 years need more attention in the future clinical trials.

scholarly journals Efficacy of immune checkpoint inhibitors for in-transit melanoma

2020 ◽  
Vol 8 (1) ◽  
pp. e000440 ◽  
Author(s):  
Emilia Nan Tie ◽  
Julia Lai-Kwon ◽  
Michael Alexander Rtshiladze ◽  
Lumine Na ◽  
James Bozzi ◽  
...  
Keyword(s):  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Single Agent ◽  
Progression Free Survival ◽  
Distant Metastases ◽  
Mek Inhibitor ◽  
Disease Recurrence ◽  
In Transit

BackgroundThe efficacy of immune checkpoint inhibitors (ICI) in metastatic melanoma is well established. However, there are limited data regarding their efficacy in in-transit melanoma (ITM). This study assessed the efficacy of ICI in patients with ITM.MethodsA retrospective review of patients with ITM commenced on an ICI between March 2013 and February 2018 at three tertiary centers in Australia. Patients were excluded if they had previous or synchronous distant metastases. Overall response rate (ORR), progression-free survival (PFS) and overall survival (OS) were based on a composite of radiological and clinical assessments.ResultsFifty-four patients were included: 27 (50%) female; median age 75 (range 26–94); 12 (22%) stage IIIB, 40 (74%) stage IIIC and 2 (4%) stage IIID; 10 (19%) BRAF mutant. Forty (74%) received single-agent anti-PD-1 (pembrolizumab or nivolumab), 8 (15%) single agent anti-CTLA-4 (ipilimumab), 5 (9%) combination anti-PD-1/anti-CTLA-4 (ipilimumab and nivolumab or pembrolizumab) and 1 (2%) combination anti-PD-L1 (atezolizumab) and MEK inhibitor (cobimetinib). The median follow-up was 15 months (2–46).ORR to ICI was 54%: 14 (26%) complete responses; 15 (28%) partial responses; 9 (17%) stable disease; 16 (30%) progressive disease. Thirteen (46%) responders had only one ITM lesion. ORR was 58% for single-agent anti-PD-1, 38% for single-agent anti-CTLA4 and 40% for anti-PD-1/anti-CTLA-4. The median PFS was 11.7 months (6.6-not reached). 1-year and 2-year PFS were 48% and 39%, respectively,. Fourteen progressed locoregionally and 11 progressed distantly. The median OS was not reached. 1-year and 2-year OS were 85% and 63%, respectively. No clinicopathological features were associated with ORR.Conclusions and relevanceICI produce objective responses in ITM and should be considered in patients with unresectable ITM or disease recurrence.

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.

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