Antibiotics prescription to decrease progression-free survival (PFS) and overall survival (OS) in patients with advanced cancers treated with PD1/PDL1 immune checkpoint inhibitors.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 3015-3015 ◽  
Author(s):  
Lisa Derosa ◽  
Bertrand Routy ◽  
Laura Mezquita ◽  
Charles Naltet ◽  
David Enot ◽  
...  
Keyword(s):  
Risk Factors ◽  
Immune Checkpoint ◽  
Cox Regression ◽  
Negative Impact ◽  
Checkpoint Inhibitors ◽  
Progression Free Survival ◽  
Cancer Type ◽  
Tumor Type ◽  
Kaplan Meier ◽  
The Impact

3015 Background: Use of antibiotics (ATB) alters the gut microbiota composition and decreases bacterial diversity. Pre-clinical evidences demonstrated the impact of the microbiota in the efficacy of immune checkpoint blockades (ICB) in cancer. Interaction between ATB and ICB has not been extensively investigated in cancer patients (pts). Our study evaluated the effect of ATB in cancer pts treated with PD-1/PD-L1 inhibitors. Methods: We conducted a retrospective analysis of pts treated with PD-1/PD-L1 inhibitors for advanced Renal Cell Carcinoma (RCC), Urothelial Cancer (UC) and Non-Small Cell Lung Cancer (NSCLC) and data on ATB use were collected. ATB(+)/(-) groups were defined as pts treated or not with ATB before (2 months period) or within the first month of ICB. PFS and OS were compared between both groups among all pts and then according to tumor site. Statistical analyses were performed using the Kaplan-Meier method. Cox regression analyses were performed separately for each cancer type adjusting for its specific risk factors. Results: Among 175 pts included, 51 (29%) received ATB (mostly beta-lactamases and fluoroquinolones). ATB(+) group had shorter PFS and OS when compared to ATB(-) group: 3.4 vs. 5.2 months, p < 0.013, and 12.2 vs. 20.8 months, p < 0.001, respectively. According to tumor type, ATB(+) group translated into decrease OS (7.0 vs. 13.8 months, p < 0.038) in NSCLC. In RCC and UC pts, ATB (+) group had shorter PFS when compared to ATB(-) group (4.3 vs. 7.4 months, p < 0.013 and 1.8 vs. 4.3 months, p = 0.048, respectively). The negative impact of ATB was maintained after multivariate analyses adjusting for risk factors in each tumor type. Conclusions: ATB prescription preceding or concomitant to the first injection of PD-1/PD-L1 inhibitors impaired the outcome in patients with advanced cancers. This reduction in efficacy seems to be independent of classical prognostic factors in RCC, UC and NSCLC. These data should be validated in larger cohort. In addition, the role of gut composition to explain this interaction is ongoing, as well as novel diagnosis tools based on microbiota to predict response/resistance to ICB.

Tissue tumor mutational burden (TMB) as a biomarker of efficacy with immune checkpoint inhibitors (ICI) in metastatic gastrointestinal (mGI) cancers.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e14559-e14559
Author(s):  
Robert William Lentz ◽  
Tyler Friedrich ◽  
Junxiao Hu ◽  
Alexis Diane Leal ◽  
Sunnie S. Kim ◽  
...  
Keyword(s):  
Checkpoint Inhibitors ◽  
Objective Response ◽  
Retrospective Chart Review ◽  
Progression Free Survival ◽  
Predictive Biomarker ◽  
Continuous Variable ◽  
Tumor Type ◽  
Logistic Regression Models ◽  
Kaplan Meier ◽  
Academic Center

e14559 Background: While TMB is very dependent on methodology, tissue TMB-H (≥10 mutations/megabase) may predict benefit with ICIs. Pembrolizumab received tissue-agnostic approval for TMB-H unresectable cancers in 2020, but little is known about TMB as a predictive biomarker in mGI cancers. We hypothesized that tissue TMB will correlate with efficacy of ICIs in mGI cancers. Methods: A retrospective chart review identified patients with mGI cancers who received an anti-PD-(L)1 drug and had known TMB at a single academic center from 2012 to 2020. The association of TMB with objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) was analyzed using the Fisher’s exact and Log-rank tests. Survival curves were generated using the Kaplan-Meier method. Cox proportional hazard and logistic regression models were used to adjust for microsatellite status. Significance was prespecified at 0.05. Results: 83 patients were identified and included. The most common cancer types were colorectal adenocarcinoma (AC, n = 29), esophageal/gastric AC (n = 21) and SCC (n = 4), cholangiocarcinoma (n = 11), anal SCC (n = 7), and pancreas AC (n = 7). Average age was 61, average number of lines of prior systemic therapy for advanced disease was 1.3 (range 0-4), and 37% of patients were treated on a clinical study. All patients received an anti-PD-(L)1 drug; 6%, 2%, and 36% also received ipilimumab, cytotoxic chemotherapy, and other combinations, respectively. Among those with esophageal/gastric cancer, 76% had known PD-L1 CPS (84% ≥1, 63% ≥5, 42% ≥10). TMB was primarily determined by Foundation One CDx (87%). TMB ranged from 0 to 54; n = 22 (27%) were TMB-H (of these, n = 10 were microsatellite instability-high (MSI-H)), and n = 61 were TMB-L ( < 10 mutations/megabase; of these, n = 2 were MSI-H). The prevalence of TMB-H and microsatellite stable (MSS) was 14.4%. TMB-L, compared to TMB-H, was associated with inferior ORR (3.5% vs 55.6%; odds ratio (OR) 0.045; p < 0.001) and PFS (median 12.7 vs 29.3 weeks; hazard ratio (HR) 2.70; p = 0.001), but not OS (HR 1.20; p = 0.60). In patients with MSS disease, TMB-L, compared to TMB-H, was associated with inferior ORR (OR 0.13; p = 0.04) but not PFS (HR 1.76; p = 0.07) or OS (HR 0.89; p = 0.79). In subgroup analyses, ORR was not significantly associated to tumor type in all or MSS patients. TMB as a continuous variable, in patients with MSS disease, was positively correlated with ORR (p = 0.02) and PFS (p = 0.04), but not OS (p = 0.59). Among all patients, PFS and OS data is immature (median follow-up 13 and 31 weeks). Conclusions: In a single center retrospective study of patients with mGI cancers treated with ICIs, TMB-H was associated with improved ORR and PFS compared to TMB-L. In patients with MSS disease, ORR remained significant. PFS and OS data are immature. TMB as a biomarker of efficacy with ICIs in mGI cancers warrants further study to guide clinical use.

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.

Effect of antibiotic use prior to or concurrent with immune checkpoint inhibitors on outcomes in patients with Hodgkin lymphoma.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 8030-8030
Author(s):  
Steven R Hwang ◽  
Alexandra Higgins ◽  
Betsy LaPlant ◽  
Matthew J. Maurer ◽  
Stephen M. Ansell ◽  
...  
Keyword(s):  
Hodgkin Lymphoma ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Cox Regression ◽  
Checkpoint Inhibitors ◽  
Retrospective Chart Review ◽  
Progression Free Survival ◽  
Antibiotic Use ◽  
Patient Specific ◽  
Cox Regression Analysis

8030 Background: There is growing interest in the identification of modifiable patient-specific factors that may predict response to immune checkpoint inhibitors (ICIs) in classical Hodgkin lymphoma (cHL). Recently, it has been proposed that antibiotic use could decrease the efficacy of ICIs in the treatment of advanced solid malignancies. The objective of our study is to assess whether antibiotic use prior to or concurrent with ICIs is associated with changes in outcomes in patients with cHL. Methods: Patients who received a PD-1 or CTLA-4 blocker for the treatment of cHL at Mayo Clinic Rochester between January 1, 2011 and October 20, 2018 were identified. We conducted a longitudinal retrospective chart review to identify those who received antibiotics within 30 or 90 days prior to initiation or concurrent with ICI therapy. Univariate cox regression analysis was used to assess for an association between antibiotic use and overall survival (OS) and progression-free survival (PFS) within these groups; a time-dependent variable was used for concurrent antibiotic use. Results: A total of sixty-two patients were identified (61% male, median age at ICI initiation 35 years [range: 19-87]). Median duration of follow up from ICI start was 38 months (range: 4-78). Twenty-one patients (34%) received antibiotics within 90 days of initiation of ICI, of which thirteen (21%) received antibiotics within 30 days. Thirty-five patients (57%) received antibiotics concurrently with ICI. Concurrent and prior antibiotic use within 90 days of ICI were both associated with inferior PFS (concurrent HR = 6.38 [95% CI 3.02-13.47]; 90-day HR = 2.21 [95% CI 1.10-4.47]) and OS (concurrent HR = 8.77 [95% CI 1.91-40.36]; 90-day HR = 2.96 [95% CI 1.09-8.04]). Conclusions: Antibiotic use is associated with inferior outcomes in patients with cHL treated with ICIs in this single institution cohort. This may reflect potential antibiotic effects on the gut microbiome (GMB) and immune system as has been suggested in prior studies. Further confirmatory studies and examination of potential confounding covariates are needed.

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.

Risk factors for myocarditis associated with immune checkpoint inhibitors using real-world clinical data.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e15100-e15100 ◽  
Author(s):  
Prantesh Jain ◽  
Jahir Gutierrez Bugarin ◽  
Avirup Guha ◽  
Chhavi Jain ◽  
Tingke Shen ◽  
...  
Keyword(s):  
Risk Factors ◽  
Liver Disease ◽  
Cancer Patients ◽  
Real World ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Cox Proportional Hazards ◽  
Cancer Type ◽  
Real World Data

e15100 Background: Immune checkpoint inhibitors (ICIs) can cause unique, high-grade immune-related adverse events. Although rare, ICI related myocarditis has the highest fatality rate (~50%). Cardiovascular monitoring is not routinely performed in patients on ICI treatment, thus risk factors remain unknown. Characterizing rare but fatal cardiac toxicities requires integration of real-world data. Methods: U.S claims data (IBM MarketScan) of over 30 million commercially insured individuals was leveraged to identify 2,687,301 cancer patients between 2011-2018. Patients ≥18 years of age treated with ICIs (targeting CTLA4 (ipilimumab) and/or the PD1 (nivolumab, pembrolizumab)/PDL1 (atezolizumab, avelumab, durvalumab) alone or in combination with ICI and/or chemotherapy were identified and followed until disenrollment. Myocarditis, comorbidities, and treatment details were identified using diagnosis and billing codes. Analyses included descriptive statistics and Cox proportional hazards regression. Results: 16,541 ICI treated cancer patients were included (median age 60; 58% male). Myocarditis was identified in 252 (1.5%) patients, majority (90%) ≥50 years old (median 63) with 12,040 person-years of follow up. 62% received anti-PD1 monotherapy, 12% anti-CTLA4, and 15% received combination treatment with other ICIs and/or chemotherapy. Most common cancer types were lung (48%), melanoma (25%), and renal cancer (14%). Cumulative incidence of myocarditis at 1 year was 2.06%; 95% CI (1.78-2.37), median onset of 80.5 days, 42% occurring within 60 days of treatment. By univariate analyses, age, cancer type, diabetes (DM), hypertension (HTN), kidney, liver disease, atrial fibrillation (AF) were related to myocarditis. Risk was lower in patients who received anti-CTLA4 monotherapy (HR: 0.490; 95% CI: 0.26-0.92; p = 0.0251). On multivariable regression analyses only age, cancer type (renal, lung cancer), comorbidities DM and liver disease were significantly associated with myocarditis (Table). Conclusions: This is the largest real-world longitudinal study for ICI associated myocarditis showing higher than reported incidence and identifiable risk factors. [Table: see text]

Impact of baseline and concomitant corticosteroid therapy on the outcomes of hepatocellular carcinoma treated with immune checkpoint inhibitor therapy.

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 531-531
Author(s):  
David James Pinato ◽  
Ahmed Omar Kaseb ◽  
Yinghong Wang ◽  
Anwaar Saeed ◽  
David Szafron ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitor ◽  
Checkpoint Inhibitors ◽  
Evaluation Criteria ◽  
Progression Free Survival ◽  
Corticosteroid Treatment ◽  
Free Survival ◽  
Checkpoint Inhibitor Therapy ◽  
The Impact

531 Background: The impact of corticosteroid treatment (CT) on the efficacy of immune checkpoint inhibitors (ICI) in hepatocellular carcinoma (HCC) is undefined. We evaluated whether CT administered at baseline (bCT) or concurrently to ICI (cCT) influences clinical outcomes of HCC patients treated with ICI. Methods: This retrospective, multi-center observational study was conducted across 9 tertiary academic referral centers collected 341 HCC patients who received ICI across 3 continents between January 1, 2016 and April 1, 2019. Outcome measures included overall (OS) and progression-free survival (PFS) calculated from time of ICI commencement and overall response rates (ORR) defined by Response Evaluation Criteria in Solid Tumors (v1.1) on 6-8 weekly periodic restaging. Results: Of 331 eligible patients, 254 (76%) had BCLC-C stage HCC and received mostly PD(L)-1 ICI monotherapy (n=250, 85%). Median OS was 12.1 months (95%CI 9.2-15.0 months) and median PFS was 8.1 months (95%CI 6.3-10 months). In total 81 patients (24%) received >10 mg prednisone equivalent daily either as bCT (n=15, 4%) or cCT (n=66, 20%). Indications for CT included procedure/prophylaxis (n=37, 45%), management of irAE (n=31, 37%), cancer-related symptoms (n=5, 2%) or comorbidities (n=8, 3%). Neither overall CT, bCT nor cCT predicted for worse OS, PFS nor ORR in uni- and multi-variable analyses (p>0.05). CT for cancer-related indications predicted for shorter PFS (2.4 vs. 11.3 months, p=0.01), OS (4.5 vs. 12.8 months, p=0.05) and reduced ORR (p=0.03) compared to cancer-unrelated indications. Conclusions: This is the first study to demonstrate that neither bCT nor cCT appear to influence response and OS following ICI in HCC. Worse survival and ORR in CT recipients for cancer-related indications appears driven by the poor prognosis associated with symptomatic HCC.

scholarly journals Identification of a N6-Methyladenosine (m6A)-Related lncRNA Signature for Predicting the Prognosis and Immune Landscape of Lung Squamous Cell Carcinoma

2021 ◽  
Vol 11 ◽  
Author(s):  
Chengyin Weng ◽  
Lina Wang ◽  
Guolong Liu ◽  
Mingmei Guan ◽  
Lin Lu
Keyword(s):  
Squamous Cell Carcinoma ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Risk Model ◽  
Cox Regression ◽  
Checkpoint Inhibitors ◽  
Lung Squamous Cell Carcinoma ◽  
Risk Groups ◽  
Immune Functions ◽  
Kaplan Meier

Backgroundm6A-related lncRNAs emerged as potential targets for tumor diagnosis and treatment. This study aimed to identify m6A-regulated lncRNAs in lung squamous cell carcinoma (LUSC) patients.Materials and MethodsRNA sequencing and the clinical data of LUSC patients were downloaded from The Cancer Genome Atlas (TCGA) database. The m6A-related lncRNAs were identified by using Pearson correlation assay. Univariate and multivariate Cox regression analyses were utilized to construct a risk model. The performance of the risk model was validated using Kaplan–Meier survival analysis and receiver operating characteristics (ROC). Immune estimation of LUSC was downloaded from TIMER, and the correlations between the risk score and various immune cells infiltration were analyzed using various methods. Differences in immune functions and expression of immune checkpoint inhibitors and m6A regulators between high-risk and low-risk groups were further explored. Finally, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were utilized to explore the biological functions of AL122125.1.ResultsA total of 351 m6A-related lncRNAs were obtained from TCGA. Seven lncRNAs demonstrated prognostic values. A further multivariate Cox regression assay constructed a risk model consisting of two lncRNAs (AL122125.1 and HORMAD2-AS1). The Kaplan–Meier analysis and area under the curve indicated that this risk model could be used to predict the prognosis of LUSC patients. The m6A-related lncRNAs were immune-associated. There were significant correlations between risk score and immune cell infiltration, immune functions, and expression of immune checkpoint inhibitors. Meanwhile, there were significant differences in the expression of m6A regulators between the high- and low-risk groups. Moreover, GO and KEGG analyses revealed that the upregulated expression of AL122125.1 was tumor-related.ConclusionIn this study, we constructed an m6A-related lncRNA risk model to predict the survival of LUSC patients. This study could provide a novel insight to the prognosis and treatment of LUSC patients.

scholarly journals Chromosomal Instability May Not Be a Predictor for Immune Checkpoint Inhibitors from a Comprehensive Bioinformatics Analysis

Life ◽  
2020 ◽  
Vol 10 (11) ◽  
pp. 276
Author(s):  
Chiao-En Wu ◽  
Da-Wei Yeh ◽  
Yi-Ru Pan ◽  
Wen-Kuan Huang ◽  
Ming-Huang Chen ◽  
...  
Keyword(s):  
Immune Checkpoint ◽  
Predictive Value ◽  
Chromosomal Instability ◽  
Immune Checkpoint Inhibitors ◽  
Bioinformatics Analysis ◽  
Checkpoint Inhibitors ◽  
P Value ◽  
Cancer Type ◽  
Significant Difference ◽  
The Impact

Immune checkpoint inhibitors (ICIs) have become the standard of care in various cancers, although their predictive tools have not yet completely developed. Here, we aimed to exam the role of 70-gene chromosomal instability signature (CIN70) in cancers, and its association with previous predictors, tumor mutation burden (TMB), and microsatellite instability (MSI), for patients undergoing ICIs, as well as the possible predictive value for ICIs. We examined the association of CIN70 with TMB and MSI, as well as the impact of these biomarkers on the survival of 33 cancer cohorts from The Cancer Genome Atlas (TCGA) databank. The predictive value of the ICIs of CIN70 in previously published reports was also validated. Using the TCGA dataset, CIN70 scores were frequently (either positively or negatively) associated with TMB, but were only significantly associated with MSI status in three types of cancer. In addition, our current study showed that all TMB, MSI, and CIN70 had their own prognostic values for survival in patients with various cancers, and that they could be cancer type-specific. In two validation cohorts (melanoma by Hugo et al. and urothelial cancer by Snyder et al.), no significant difference of CIN70 scores was found between responders and non-responders (p-value = 0.226 and 0.108, respectively). In addition, no overall survival difference was noted between patients with a high CIN70 and those with a low CIN70 (p-value = 0.106 and 0.222, respectively). In conclusion, the current study, through a comprehensive bioinformatics analysis, demonstrated a correlation between CIN70 and TMB, but CIN70 is not the predictor for cancer patients undergoing ICIs. Future prospective studies are warranted to validate these findings.

scholarly journals Comparison of RECIST 1.1 and iRECIST in Patients Treated with Immune Checkpoint Inhibitors: A Systematic Review and Meta-Analysis

Cancers ◽  
2021 ◽  
Vol 13 (1) ◽  
pp. 120
Author(s):  
Hyo Jung Park ◽  
Gun Ha Kim ◽  
Kyung Won Kim ◽  
Choong Wook Lee ◽  
Shinkyo Yoon ◽  
...  
Keyword(s):  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Meta Analysis ◽  
Progression Free Survival ◽  
Recist 1.1 ◽  
Rate Ratios ◽  
A Minor ◽  
Survival Endpoint ◽  
The Impact

Despite wide recognition of iRECIST, evidence regarding the impact of iRECIST over RECIST 1.1 is lacking. We aimed to evaluate the impact of iRECIST on assessing treatment efficacy of immune checkpoint inhibitors (ICIs) over RECIST 1.1. Articles that evaluated the treatment response and outcome based on both RECIST 1.1 and iRECIST were eligible. Data regarding overall response rates (ORR) and disease control rate (DCR) based on RECIST 1.1 and iRECIST, and data required to estimate individual patient data of progression-free survival (PFS) were extracted. Estimates were compared using meta-regression and pooled incidence rate ratios. The pooled difference of restricted mean survival time (RMST) of PFS between two criteria were calculated. Eleven studies with 6210 patients were analyzed. The application of iRECIST had no impact on the response-related endpoint by showing no significantly different ORR and DCR from RECIST 1.1 (pooled ORR, 23.6% and 24.7% [p = 0.72]; pooled DCR, 45.3% and 48.7% [p = 0.56] for iRECIST and RECIST 1.1, respectively) and had a minor impact on a survival endpoint by showing longer RMST of PFS than RECIST 1.1 (pooled difference, 0.46 months; 95% CI, 0.10–0.82 months; p = 0.01). Such a modest benefit of iRECIST should be considered when we design a clinical trial for immune checkpoint inhibitors.

scholarly journals Timing of steroid initiation and response rates to immune checkpoint inhibitors in metastatic cancer

2021 ◽  
Vol 9 (7) ◽  
pp. e002261
Author(s):  
Diana V Maslov ◽  
Karine Tawagi ◽  
Madhav KC ◽  
Victoria Simenson ◽  
Helen Yuan ◽  
...  
Keyword(s):  
Survival Data ◽  
Immune Checkpoint ◽  
Cell Function ◽  
Checkpoint Inhibitors ◽  
Metastatic Cancer ◽  
Objective Response ◽  
P Value ◽  
Cancer Type ◽  
Tumor Type ◽  
Treatment Type

BackgroundCorticosteroids (CS) are the mainstay of immune-related adverse effect (irAE) management, as well as for other indications in cancer treatment. Previous studies evaluating whether CS affect immune checkpoint inhibitor (CPI) efficacy compared patients receiving CS versus no CS. However, there is a paucity of clinical data evaluating the timing of concomitant CS and CPI efficacy.MethodsWe retrospectively collected data from patients who received CS during CPI treatment at a single institution. Patients were in two cohorts based on timing of initiation of CS (≥2 months vs <2 months after initiating CPI). Patient characteristics, irAEs, cancer type, treatment type, treatment response/progression per RECIST V.1.1, and survival data were collected. Kaplan-Meier and Cox proportional hazard regression methods estimated HRs for the primary endpoint of progression-free survival (PFS) along with overall survival (OS).ResultsWe identified 247 patients with metastatic cancer who received CS concurrently with CPIs. The median time on CS was 1.8 months. After adjusting for treatment type, tumor type, brain metastases, and irAEs, those treated with CS ≥2 months after starting CPI had a statistically significant longer PFS (HR=0.30, p<0.001), and OS (HR 0.34, p<0.0001) than those who received CS <2 months after starting CPI. Objective response rate (ORR) for patients on CS ≥2 months was 39.8%, versus ORR for patients <2 months was 14.7% (p value =<0.001)ConclusionOur results suggest that early use of CS during CPI treatment significantly hinders CPI efficacy. This data needs to be validated prospectively. Future studies should focus on the immune mechanisms by which CSs affect T-cell function early in the CPI treatment course.

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