A pan-cancer analysis of ARID1A as a potential biomarker for immune checkpoint therapy.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 3540-3540
Author(s):  
Dongyong Yang ◽  
Yuan Xu ◽  
Linlin Huang ◽  
Zhifeng Guo ◽  
Jimin Fan ◽  
...  
Keyword(s):  
Cancer Patients ◽  
Gene Mutation ◽  
Immune Checkpoint ◽  
Immune Checkpoint Blockade ◽  
Study Cohort ◽  
Tumor Type ◽  
Significant Difference ◽  
Chinese Cohort ◽  
Ngs Data ◽  
Pan Cancer

3540 Background: AT-rich interactive domain 1A (ARID1A), encoding a subunit of the BAF (SWI/SNF) chromatin remodeling complex, is correlated with the origination and progress of tumor. Previous research on ARID1A gene revealed that ARID1A deficiency was associated with mismatch repair (MMR) and higher tumor mutation burden (TMB) level in cancer, which might cooperate with immune checkpoint blockade therapy. Methods: Next generation sequencing (NGS) data of 10336 pan-cancer patients were obtained from the MSK-IMPACT Clinical Sequencing cohort (MSKCC). NGS data of 15849 pan-cancer patients from Chinese clinical dataset were analyzed to explore the association between ARID1A gene mutation and TMB. TMB was defined as total number of somatic non-synonymous mutations in coding region. 853 advanced NSCLC patients from two independent cohorts (OAK study cohort and POPLAR study cohort) were used to analyze the correlation between ARID1A alteration and the efficacy of immune checkpoint blockade immunotherapies (ICIs). Results: In total, 8.62% (891/10336) of pan-cancer patients in MSKCC harbored ARID1A mutation and 8.47% (3188/37628) in Chinese cohort. In MSKCC cohort, the highest ARID1A mutation frequency tumor type was endometrial cancer (31.64%, 69/218), bladder cancer (26.95%, 114/423) and hepatobiliary cancer (17.18%, 61/355) come in second and third, respectively. While in Chinese cohort, the top three ARID1A mutation frequency tumor types were endometrial cancer (39.29%, 88/224), gastric carcinoma (17.80%, 318/1787) and urothelial carcinoma (17.18%, 83/483), respectively. ARID1A gene mutation was also associated with higher TMB in the Chinese pan-cancer cohort (P < 0.0001). The highest medium TMB level of ARID1A mutation tumor type was Urothelial carcinoma with 18.63 Muts/Mb (n = 65). In addition, the TMB level and prognositic analysis were performed on patients in two independent NSCLC cohorts with ICIs, TMB level of ARID1A mutant group was higher than wild-type group with significant difference (P < 0.0001). The overall survival (OS) of ARID1A mutation group were significantly shorter than wild-type group (OS, median, 6.80 vs 10.28 months; HR, 1.47; P = 0.0474), and a decreasing trend on progression-free survival (PFS) without significant difference (median, 1.46 vs 2.99 months; HR, 1.27; P = 0.1584). Conclusions: The results indicated that ARID1A gene mutation was associated with a higher TMB level in Chinese pan-cancer patients, and patients harboring these genes mutations might easily benefit from ICIs.

Hepatocellular carcinoma with ARID1A mutation is associated with higher TMB and poor survival.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e16667-e16667 ◽  
Author(s):  
Yaorong Peng ◽  
Bowen Gao ◽  
Zhenyu Zhou ◽  
Tingting Chen ◽  
Wenzhuan Xie ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cancer Patients ◽  
Gene Mutation ◽  
Sequencing Data ◽  
Coding Region ◽  
Poor Prognostic Factor ◽  
Synonymous Mutations ◽  
Significant Difference ◽  
Chinese Cohort ◽  
Pan Cancer

e16667 Background: Hepatocellular carcinoma (HCC) is a heterogeneous disease that lacks molecular predictors of response to available treatments. AT-rich interactive domain 1A (ARID1A), a SWI/SNF chromatin remodeling gene, is commonly mutated in human cancers and hypothesized to be a tumor suppressor gene. In recent years, immune checkpoint blockade immunotherapies (ICIs) are promising therapies for multiple cancers including HCC, and tumor mutation burden (TMB) was an important biomarker to predict the efficacy of ICIs. Besides, previous research reported that ARID1A deficiency was associated with mismatch repair (MMR) in cancer, and may cooperated with ICIs. Methods: Whole exome sequencing data of 10336 pan-cancer patients including 353 HCC patients was obtained from the Cancer Genome Altas (TCGA). Next generation sequencing (NGS) data of 15849 pan-cancer patients including 1926 HCC patients from Chinese clinical dataset were analyzed to explore the correlation between ARID1A gene mutation and TMB. TMB was defined as total number of somatic non-synonymous mutations in coding region. Prognostic data of 136 HCC patients were obtained from the MSK-IMPACT Clinical Sequencing Cohort (MSKCC). Results: In total, 8.62% (891/10336) of pan-cancer patients in TCGA harboring ARID1A mutation and 8.47% (3188/37628) in Chinese cohort, while mutant percentage of HCC was 9.35% (33/353) in TCGA, 9.03% (174/1926) in Chinese cohort, the alternation frequency of ARID1A in two cohorts was no significant difference (P = 0.3334). The medium TMB level of ARID1A mutant group was higher than wild-type group with significant difference both in Chinese pan-cancer and HCC (medium TMB level, P < 0.0001). Results of 18 kinds of ARID1A mutated tumors patients in TCGA cohort indicated that ARID1A mutation was an independent risk factor in liver cancer affecting overall survival (OS, HR 2.43, 95% IC 1.07-5.54, P = 0.0286). Besides, Kaplan-Meier analysis was performed on HCC patients in MSKCC cohort, ARID1A statue resulted in significantly shorter OS (median, 12.2 vs 21.43 months; HR 2.5; P = 0.0092). Conclusions: The results indicated that ARID1A gene mutation was a poor prognostic factor in hepatocellular carcinoma, and these mutational states were associated with higher TMB level, which might be a potential positive biomarker of immunotherapy.

Correlation of HLA-B*35 and DRB1*11 alleles with a high risk of interstitial aseptic pneumonitis in cancer patients receiving PD-1/PDL1 immune-checkpoint blockade.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e15094-e15094
Author(s):  
Pierpaolo Correale ◽  
Rita Emilena Saladino ◽  
Giovanna Bianco ◽  
Alessia Stranges ◽  
Diana Giannarelli ◽  
...  
Keyword(s):  
Cancer Patients ◽  
Immune Checkpoint ◽  
Dna Typing ◽  
Metronomic Chemotherapy ◽  
Immune Checkpoint Blockade ◽  
Checkpoint Blockade ◽  
Tumor Type ◽  
Chi Square ◽  
Recommended Treatment ◽  
Chi Square Test

e15094 Background: Tumor infiltrating CTL-rescue by PD-1/PDL1 immune-checkpoint blockade is a recommended treatment for several malignancies including non-small-cell-lung-cancer (NSCLC), malignant melanoma, head and neck, kidney, and urothelial cancer. MAbs to either PD-1 (Nivolumab and Pembrolizumab) or PDL1 (Atezolizumab and Durvalumab) are considered as active drugs in these patients, however, their use may be complicated by unpredictable immune-related adverse events (irAEs) and in less extent by a dreaded interstitial aseptic pneumonitis (IAP). Methods: We carried out a retrospective multi-institutional analysis aimed to investigate possible clinical and biological parameters correlated with the occurrence of IAP in a cohort of 256 cancer patients (188 with mNSCLC and 78 with other malignancies) who received PD-1/PDL-1 blockade since November 2015. Association of IAP with clinical/biological factors was assessed by the chi-square test. Statistics were performed by the SPSS software 23.0. HLA molecular analysis was performed by reverse SSO DNA typing assays on patients’ PBMCs. Results: A centralised radiological review recorded a IAP in 29 patients (11.3%) whose 15 (5.8%) were free of symptoms. There was no correlation of IAP risk with tumor type, specific PD-1 or PDL1 blocking mAb, radiation therapy, inflammatory markers, and other irAEs. IAP was more frequent in males than females [RR = 2.03, (95% CI: 0.63-5.61) p > 0.05] and occurred more often in mNSCLC patients who had received metronomic chemotherapy +/- bevacizumab [RR = 3.05 (95% CI: 1.32-7.06),P = 0.005] or TKI [RR = 1.73 (95% CI: 0.75-4.00),P > 0.05] compared with other treatments prior PD-1/PDL1 blockade. Finally, IAP occurrence was strictly correlated to the expression of HLA-B*35 [RR = 1.73 (95% CI: 0.81-3.71) P < 0.05] and DRB1*11 [RR = 2.34 (95% CI: 1.02-5.39); P = 0.03], two alleles associated to common autoimmune diseases. Conclusions: Taken together, our findings may have relevant implications in predicting the risk of IAP in mNSCLC receiving PD-1/PDL1 blockade and provide the rationale for further immunological and clinical investigations.

scholarly journals Treatment with therapeutic anticoagulation is not associated with immunotherapy response in advanced cancer patients

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Paul Johannet ◽  
Amelia Sawyers ◽  
Nicholas Gulati ◽  
Douglas Donnelly ◽  
Samuel Kozloff ◽  
...  
Keyword(s):  
Cancer Patients ◽  
Advanced Cancer ◽  
Immune Checkpoint ◽  
Checkpoint Inhibitors ◽  
Objective Response ◽  
Progression Free Survival ◽  
Immune Checkpoint Blockade ◽  
Coagulation Cascade ◽  
Advanced Cancer Patients ◽  
Clinical Endpoints

Abstract Background Recent preclinical data suggest that there may be therapeutic synergy between immune checkpoint blockade and inhibition of the coagulation cascade. Here, we investigate whether patients who received immune checkpoint inhibitors (ICI) and were on concomitant anticoagulation (AC) experienced better treatment outcomes than individuals not on AC.Affiliation: Kindly confirm if corresponding authors affiliation is identified correctly.The corresponding author's affiliation is correct. Methods We studied a cohort of 728 advanced cancer patients who received 948 lines of ICI at NYU (2010–2020). Patients were classified based on whether they did (n = 120) or did not (n = 828) receive therapeutic AC at any point during their treatment with ICI. We investigated the relationship between AC status and multiple clinical endpoints including best overall response (BOR), objective response rate (ORR), disease control rate (DCR), progression free survival (PFS), overall survival (OS), and the incidence of bleeding complications.Affiliations: Journal instruction requires a country for affiliations; however, this is missing in affiliations 1 to 5. Please verify if the provided country is correct and amend if necessary.The country is correct for all affiliations (1 - 5). Results Treatment with AC was not associated with significantly different BOR (P = 0.80), ORR (P =0.60), DCR (P =0.77), PFS (P = 0.59), or OS (P =0.64). Patients who received AC were significantly more likely to suffer a major or clinically relevant minor bleed (P = 0.05). Conclusion AC does not appear to impact the activity or efficacy of ICI in advanced cancer patients. On the basis of our findings, we caution that there is insufficient evidence to support prospectively evaluating the combination of AC and immunotherapy.

scholarly journals 700 Increasing MHC-I expression to potentiate immune checkpoint blockade therapy

2021 ◽  
Vol 9 (Suppl 3) ◽  
pp. A728-A728
Author(s):  
Shengqing Gu ◽  
Wubing Zhang ◽  
Xiaoqing Wang ◽  
Peng Jiang ◽  
Nicole Traugh ◽  
...  
Keyword(s):  
T Cell ◽  
Cancer Cells ◽  
Cancer Patients ◽  
Immune Checkpoint ◽  
Immune Checkpoint Blockade ◽  
Checkpoint Blockade ◽  
Mhc I ◽  
Expression Signature ◽  
Smac Mimetics ◽  
Smac Mimetic

BackgroundCancer immunotherapy, especially immune checkpoint blockade (ICB) therapy, is leading to a paradigm shift in cancer treatment, as a small percentage of cancer patients have obtained durable remission following ICB treatment. Successful ICB responses rely on cancer cells presenting antigens to the cell surface via the major histocompatibility complex (MHC), which activates antigen-specific T-lymphocytes to kill cancer cells. Type-I MHC (MHC-I) is wildly expressed in all cell types and mediates the interaction with cytotoxic CD8 T cells. However, over 65% of cancer patients are estimated to show defects in MHC-I-mediated antigen presentation, including downregulation of its expression that can lead to primary or acquired resistance to ICB therapy, and therapeutic strategies to effectively restore or boost MHC-I are limited.MethodsHere, we employed a CRISPR screening approach with dual-marker FACS sorting to identify factors that decouple the regulation of MHC-I and PD-L1. The experimentally validated target was used to generate a KO differential expression signature. Using this signature, we analyzed transcriptome data from drug perturbation studies to identify drugs that regulate MHC-I but not PD-L1. Finally, we validated the effect of the identified drug to enhance ICB response in a T-cell-dependent manner in vivo.ResultsCRISPR screens identified TRAF3, a suppressor of the NF-κB pathway, as a negative regulator of MHC-I but not PD-L1. The Traf3-knockout (Traf3-KO) gene expression signature is associated with better survival in ICB-naive cancer patients and better ICB response. We then screened for drugs with similar transcriptional effects as this signature and identified SMAC mimetics. We experimentally validated that the SMAC mimetic birinapant upregulates MHC-I, sensitizes cancer cells to T-cell-dependent killing, and adds to ICB efficacy. However, in cancer cells with high NF-κB activity, the effect of birinapant on MHC-I is weak, indicating context-dependent MHC-I regulation.ConclusionsIn summary, Traf3 deletion specifically upregulates MHC-I without inducing PD-L1 in response to various cytokines and sensitizes cancer cells to T-cell-driven cytotoxicity. The SMAC mimetic birinapant phenocopies Traf3-knockout and sensitizes MHC-I-low melanoma to ICB therapy. Further studies are needed to elucidate the context-dependencies of MHC-I regulation. Our findings provide preclinical rationale for treating some tumors expressing low MHC-I with SMAC mimetics to enhance sensitivity to immunotherapy. The approach used in this study can be generalized to identify other drugs that enhance immunotherapy efficacy.AcknowledgementsThis study was supported by grants from the NIH (R01CA234018 to XSL, R01AI137337 to BEG, P50CA101942-12 and P50CA206963 to GJF), Breast Cancer Research Foundation (BCRF-19-100 to XSL), Burroughs Wellcome Career Award in Medical Sciences (to BEG), and Sara Elizabeth O'Brien Trust Fellowship (to SG).We thank Drs. Kai Wucherpfennig and Deng Pan for their insightful suggestions on this study.Ethics ApprovalAll mice were housed in standard cage in Dana-Farber Cancer Institute Animal Resources Facility (ARF). All animal procedures were carried out under the ARF Institutional Animal Care and Use Committee (IACUC) protocol and were in accordance with the IACUC standards for the welfare of animals.

A pan-cancer study on characteristic of CDK4/6 amplification between Chinese and Western patients.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e15074-e15074
Author(s):  
Yamin Zhang ◽  
Zilin Cui ◽  
Rui Shi ◽  
Xiaolong Liu ◽  
Yang Li ◽  
...  
Keyword(s):  
Soft Tissue ◽  
Liver Cancer ◽  
Soft Tissue Sarcoma ◽  
Lung Adenocarcinoma ◽  
Ovarian Carcinoma ◽  
Cancer Patients ◽  
Stomach Carcinoma ◽  
Chinese Cohort ◽  
Cancer Types ◽  
Pan Cancer

e15074 Background: CDK4/6 kinases associate with cyclin D proteins during transition from G1 to S phase of the cell cycle. Amplification of CDK4/6 may elicit the activity of cyclin D, which hyperphosphorylates RB, ultimately leading to uncontrolled cell proliferation. Currently, three CDK4/6 inhibitors are used in breast cancer, ovarian cancer and sarcoma. Herein, we investigate the prevalence of CDK4/6 amplification in Chinese and Western cancer patients, hope to find more cancer subtypes with CDK4/6 amplification. Methods: Next-generation sequencing data and clinical data were collected from 10828 TCGA pan-cancer patients (Western cohort). A 539-gene panel targeted sequencing assay was performed on FFPE tumor samples from 4181 Chinese pan-cancer patients (Chinese cohort). CDK4 and CDK6 amplification were calculated on the two cohorts following the same criteria. Results: In total, 182 (4.4%) of the 4181 Chinese patients and 529 (4.9%) of the 10828 Western patients had CDK4 amplification, 133 (3.2%) of the 4181 Chinese patients and 475 (4.4%) of the 10828 Western patients had CDK6 amplification. In Western cohort, the top 5 CDK4 amplification-associated cancer types were sarcoma, glioblastoma multiforme, lung adenocarcinoma, ovarian carcinoma, and adrenocortical carcinoma, and the top 5 CDK6 amplification-associated cancer types were esophageal carcinoma, ovarian carcinoma, lung squamous cell carcinoma, stomach adenocarcinoma, sarcoma. In Chinese cohort, the top 5 CDK4 amplification-associated cancer types were lung adenocarcinoma, melanoma, sarcoma, stomach carcinoma, liver cancer, and the top 5 CDK6 amplification-associated cancer types were lung adenocarcinoma, stomach carcinoma, liver cancer, melanoma, glioma. In addition, CDK4 amplification in Chinese cohort, 22 (11%) of the 203 Chinese bone and soft tissue sarcoma patients had CDK4 amplification, and 4 (2%) of the 203 had CDK6 amplification. Bone and soft tissue sarcoma types with CDK4 / 6 amplification including soft tissue sarcoma, bone cancer, fibrosarcoma, chondrosarcoma, rhabdomyosarcoma, liposarcoma, synovial sarcoma. Conclusions: Our study provided a characteristic of CDK4/6 amplification in Chinese and Western pan-cancer patients. Analysis revealed frequent CDK4 / 6 amplification in lung cancer, sarcoma, stomach carcinoma, ovarian carcinoma and liver cancer. It is suggested patient with these cancer types may potentially benefit from CDK4/6 inhibitor.

scholarly journals Tumor copy-number alterations predict response to immune-checkpoint-blockade in gastrointestinal cancer

2020 ◽  
Vol 8 (2) ◽  
pp. e000374 ◽  
Author(s):  
Zhihao Lu ◽  
Huan Chen ◽  
Shuang Li ◽  
Jifang Gong ◽  
Jian Li ◽  
...  
Keyword(s):  
Cancer Patients ◽  
Immune Checkpoint ◽  
Clinical Benefit ◽  
Copy Number ◽  
Validation Cohort ◽  
Predictive Biomarkers ◽  
Immune Checkpoint Blockade ◽  
Checkpoint Blockade ◽  
Copy Number Alterations ◽  
Gi Cancer

BackgroundDespite the great achievements made in immune-checkpoint-blockade (ICB) in cancer therapy, there are no effective predictive biomarkers in gastrointestinal (GI) cancer.MethodsThis study included 93 metastatic GI patients treated with ICBs. The first cohort comprising 73 GI cancer patients were randomly assigned into discovery (n=44) and validation (n=29) cohorts. Comprehensive genomic profiling was performed on all samples to determine tumor mutational burden (TMB) and copy-number alterations (CNAs). A subset of samples was collected for RNA immune oncology (IO) panel sequencing, microsatellite instability (MSI)/mismatch repair and program death ligand 1 (PD-L1) expression evaluation. In addition, 20 gastric cancer (GC) patients were recruited as the second validation cohort.ResultsIn the first cohort of 73 GI cancer patients, a lower burden of CNA was observed in patients with durable clinical benefit (DCB). In both the discovery (n=44) and validation (n=29) subsets, lower burden of CNA was associated with an improved clinical benefit and better overall survival (OS). Efficacy also correlated with a higher TMB. Of note, a combinatorial biomarker of TMB and CNA may better stratify DCB patients from ICB treatment, which was further confirmed in the second validation cohort of 20 GC patients. Finally, patients with lower burden of CNA revealed increased immune signatures in our cohort and The Cancer Genome Atlas data sets as well.ConclusionsOur results suggest that the burden of CNA may have superior predictive value compared with other signatures, including PD-L1, MSI and TMB. The joint biomarker of CNA burden and TMB may better stratify DCB patients, thereby providing a rational choice for GI patients treated with ICBs.

scholarly journals Role of tumor gene mutations in treatment response to immune checkpoint blockades

2019 ◽  
Vol 2 (2) ◽  
pp. 100-109 ◽  
Author(s):  
Manni Wang ◽  
Liu Yu ◽  
Xiawei Wei ◽  
Yuquan Wei
Keyword(s):  
Gene Expression ◽  
Treatment Response ◽  
Cancer Patients ◽  
Tumor Cells ◽  
Immune Checkpoint ◽  
Gene Mutations ◽  
Immune Checkpoint Blockade ◽  
Recent Developments ◽  
Tumor Gene

AbstractEarly studies shed light on the immune suppression of immune checkpoint molecules in the cancer microenvironment, with later studies applying immune checkpoint blockade (ICB) in treatment of various malignancies. Despite the encouraging efficacy of ICBs in a substantial subset of cancer patients, the treatment response varies. Gene mutations of both tumor cells and immune cells in the tumor microenvironment have recently been identified as potential predictors of the ICB response. Recent developments in gene expression profiling of tumors have allowed identification of a panel of mutated genes that may affect tumor cell response to ICB treatment. In this review, we discuss the association of the ICB response with gene expression and mutation profiles in tumor cells, which it is hoped will help to optimize the clinical application of ICBs in cancer patients.

Sequence of stereotactic ablative radiotherapy and immune checkpoint blockade in the treatment of metastatic lung cancer.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e20665-e20665 ◽  
Author(s):  
Ramya Pinnamaneni ◽  
Aparna Madhukeshwar Hegde ◽  
Sulochana Devi Cherukuri ◽  
Hyder Husain Arastu ◽  
Mark Bowling ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Overall Survival ◽  
Cancer Patients ◽  
Immune Checkpoint ◽  
Synergistic Effects ◽  
Immune Checkpoint Blockade ◽  
Advanced Lung Cancer ◽  
Stereotactic Ablative Radiotherapy ◽  
Lung Cancer Patients ◽  
Immune Checkpoint Proteins

e20665 Background: Monoclonal antibodies targeting immune checkpoint proteins have recently been shown to elicit robust and durable responses in patients with advanced lung cancer. However, with response rates ranging from 15-20%, immunomodulatory strategies are needed to improve outcomes. Stereotactic ablative radiotherapy (SABR) may be a promising immunomodulatory strategy given its synergistic effects without added toxicity. Several pre-clinical trials combining SABR and immunotherapy have shown improvement in progression free and overall survival. Given this, it has been our multidisciplinary programmatic approach to bring in SABR in patients receiving immunotherapy for a potential immune boost. Methods: This is a retrospective study evaluating the overall survival (OS) of all lung cancer patients who received Nivolumab with SABR at our institution. We included lung cancer patients of all pathologic subtypes who received Nivolumab. We identified patients who received SABR, to sites of symptomatic metastatic disease, within 30 days preceding (Before) or during (Sandwich) Nivolumab treatment. Results: Out of 76 lung cancer patients treated with Nivolumab, 22 received RT- 10 Before and 12 Sandwich. At a median follow up time of 10.6 months (mo), median OS for patients with no RT was 4.8 mo, Before was 5.2 mo and Sandwich was not reached (NR) (p = 0.06). The 1 year OS for the Sandwich arm was 52.1%. When compared to no RT, the Before arm had a statistically insignificant reduction in mortality (HR 0.59, 95% CI 0.25 – 1.41, p = 0.24). The Sandwich arm had a statistically significant reduction in mortality (HR 0.37, 95% CI 0.14 – 0.94, p = 0.04). Conclusions: There is an improvement in OS when SABR is administered as a Sandwich approach during Nivolumab treatment, likely due to SABR-induced neoantigen release, increased PDL1 expression and subsequent abscopal effect. Further prospective studies are needed to evaluate optimal sequencing, dose and site of RT with immunotherapy. [Table: see text]

Cumulative steroid doses and response rates to immune checkpoint inhibitors in metastatic cancer.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e15133-e15133
Author(s):  
Karine Tawagi ◽  
Diana Maslov ◽  
Victoria Simenson ◽  
Helen Yuan ◽  
Cameron Parent ◽  
...  
Keyword(s):  
Immune Checkpoint ◽  
Checkpoint Inhibitors ◽  
Smoking Status ◽  
Metastatic Cancer ◽  
Stage Iv ◽  
Progression Free Survival ◽  
Response Rates ◽  
Tumor Type ◽  
Significant Difference ◽  
Cox Proportional Hazard Regression

e15133 Background: Steroids are the mainstay of immune-related adverse effect (irAE) management, as well as for other indications in cancer treatment. Previous studies evaluating whether steroids have an effect on immune checkpoint inhibitor (CPI) efficacy compared patients receiving steroids vs. no steroids. This comparison may be confounded by different rates of irAEs and a known association of irAEs with higher response rates to CPIs. There is a paucity of CPI efficacy data in relation to the total dose of concomitant steroids. Methods: We retrospectively collected data from patients treated with CPIs alone, who received steroids during their CPI treatment at a single institution. IrAEs were defined using the CTCAEv5 criteria. Response rate (RR) and progression were defined per RECIST v1.1. Kaplan Meier and Cox proportional hazard regression methods were used to estimate the survival probability and hazard ratios (HR). Results: We identified 260 patients with stage IV cancer who received steroids concurrently with CPI treatment. A total of 111 patients (42.7%) received ≥1000mg prednisone equivalence during the course of their CPI treatment, and the remaining 149 patients (57.3%) received < 1000mg PED. There was no difference in progression free survival (PFS) between the two cohorts [HR of 0.923 for < 1000 mg PED group; p = 0.6016] or in overall survival (OS) [0.854 for < 1000 mg PED group, p = 0.3308]. Median PFS for the < 1000mg group was 5.9 months (mo), vs 6.3 mo in the ≥1000mg group. Median OS for the < 1000mg group was 15.76 mo, vs 11.53 mo in the ≥1000mg group. The RR was numerically higher in the prednisone < 1000mg cohort at 29.53% vs 20.72% in the ≥1000mg cohort, however not statistically significant (p = 0.1082). Basic characteristics including sex, race, tumor type, and smoking status, were similar between the two groups. There was a statistically significant difference in BMI distribution and steroid indication (irAE indication higher in >1000 mg PED cohort than non-irAE) between the two groups. Conclusions: PFS, OS, and RR were not different between patients who received >1000mg vs. < 1000mg PED during CPI therapy. These data suggest that even high doses and protracted courses of corticosteroids may not hinder CPI efficacy. However, differences in our primary endpoint PFS may be confounded by difference in BMI and rates of irAEs between each cohort, which are both known to be associated with improved CPI efficacy. Further analyses to account for these differences along with how timing of steroid initiation affects CPI-efficacy will be completed by time of presentation.

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