Prognostic value of KRAS mutation in advanced non-small-cell lung cancer treated with immune checkpoint inhibitors: A meta-analysis and review.
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ABSTRACT:
SUBMITTER: Kim JH
PROVIDER: S-EPMC5564642 | biostudies-other | 2017 Jul
REPOSITORIES: biostudies-other
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Project description:BackgroundImmune checkpoint inhibitors (ICIs) represent a paradigm shift in the development of cancer therapy. However, the improved efficacy of ICIs remains to be further investigated. We conducted a systematic review and meta-analysis to evaluate the pan-immunoinflammatory value (PIV) and PILE score used to predict response to ICI therapy.MethodsWe searched selected databases for studies on pan-immune inflammation values and their association with outcomes of treatment with immune checkpoint inhibitors. We used hazard ratios (HRS) and 95% confidence intervals (CI) to summarize survival outcomes. All data analyses were performed using STATA 15.0.Results7 studies comprising 982 patients were included in the meta-analysis. The pooled results showed that higher PIV was significantly associated with shorter overall survival OS (HR = 1.895, 95%CI: 1.548-2.318) and progression-free survival (PFS) (HR = 1.582, 95%CI: 1.324-1.890). Subgroup analyses also confirmed the reliability of the results.ConclusionsHigh PIV and PILE metrics are associated with lower survival in cancer patients receiving ICIs.
| S-EPMC10895004 | biostudies-literature
Project description:Few prognostic factors have been identified in patients with metastatic urothelial carcinoma (mUC) treated with immune checkpoint inhibitors (ICIs). The Lung Immune Prognostic Index (LIPI) was associated with clinical outcomes for ICIs in several tumor types. We aim to assess the value of the LIPI in patients with mUC treated with ICIs. A retrospective ICI cohort and a validation cohort (SAUL cohort) included, respectively, patients with mUC treated with ICI in 8 European centers (any line) and patients treated with atezolizumab in a second or further line. A chemotherapy-only cohort was also analyzed. The LIPI score was based on 2 factors, derived neutrophils/(leukocytes minus neutrophils) ratio (dNLR) > 3 and lactate dehydrogenase > upper limit of normal, and defined 3 prognostic groups. The association of LIPI with progression-free survival (PFS) and overall survival (OS) was assessed. In the ICI and SAUL cohorts, 137 and 541 patients were respectively analyzed. In the ICI cohort, mPFS and mOS were 3.6 mo (95% CI; 2.6-6.0) and 13.8 mo (95% CI; 11.5-23.2) whereas in the SAUL cohort the mPFS and mOS were 2.2 mo (95% CI; 2.1-2.3) and 8.7 mo (95% CI; 7.8-9.9) respectively. The LIPI classified the population of these cohorts in good (56%; 52%), intermediate (35%; 36%) and poor (9%; 12%) prognostic groups (values for the ICI and SAUL cohorts respectively). Poor LIPI was associated with a poorer OS in both cohorts: hazard ratio (HR) for the ICI cohort = 2.69 (95% CI; 1.24-5.84, p = 0.035); HR = 2. 89 for the SAUL cohort (CI 95%: 1.93-4.32, p < 0.0001). Similar results were found in the chemo cohort. The LIPI score allows to identify different subgroups in patients with good prognostis according to the Bellmunt score criteria, with a subset of patients with poorer outcomes having an mOS of 3.7 mo compared to the good and intermediate LIPI subgroups with mOS of 17.9 and 7.4 mo, respectively. The LIPI score was associated with survival in mUC patients treated by ICIs. Future prospective studies will be required to test the combination of Bellmunt score and the LIPI score as a more accurate prognosis tool.
| S-EPMC9954148 | biostudies-literature
Project description:Accumulating interest has been surging over the past few years regarding the effects of obesity on immunotherapy. In addition to the body mass index (BMI), imaging-quantified body fat compartments have been investigated. The present study aimed to evaluate the predictive value of the BMI and computed tomography (CT)-based body fat in patients with cancer receiving immunotherapy. For this purpose, the PubMed, MEDLINE, EMBASE and Cochrane databases were searched from January 2017 to July 2022. Clinical studies evaluating the association between BMI or body fat and survival of patients with cancer treated with immune checkpoint inhibitors (ICIs) were included. In total, 15 studies reporting on the BMI were included in the meta-analysis and 16 studies evaluating body fat were included in the systematic review. According to the classification of the World Health Organization, overweight and obese patients with ICI treatment showed improved overall survival [overweight vs. normal: Hazard ratio (HR)=0.79, 95% confidence interval (CI)=0.64-0.98, P=0.03; obese vs. normal: HR=0.75, 95% CI=0.60-0.94, P=0.013] and progression-free survival (overweight vs. normal: HR=0.82, 95% CI=0.70-0.97, P=0.02; obese vs. normal: HR=0.81, 95% CI=0.65-1.02, P=0.07). Among the articles investigating the effect of body fat composition on the efficacy of immunotherapy, a number of studies included various CT analysis techniques and cutoffs to define body fat composition. Associations of body fat with survival were contradictory in different patients with cancer treated with immunotherapy. Obesity was associated with better survival in patients with cancer treated with ICIs. Further analyses are required to demonstrate the prognostic value of body fat in patients with cancer immunotherapy.
| S-EPMC10729294 | biostudies-literature
Project description:BackgroundPlasma D-dimer is of great significance for the clinical exclusion of tumor-related thrombosis. Previous studies have shown its predictive role in non-small cell lung cancer (NSCLC) treated with chemotherapy. However, whether pretreatment D-dimer could predict the efficacy and prognosis in NSCLC patients treated with immune checkpoint inhibitors (ICIs) remains unclear.MethodsAdvanced NSCLC patients treated with ICIs at the Chinese PLA General Hospital between January 2015 and March 2019 were enrolled. Patients were divided into a pretreatment normal D-dimer group (≤0.5 µg/mL) and high D-dimer group (>0.5 µg/mL). Optimization-based approach was applied to balance baseline covariates between the 2 groups, including age, sex, histological type, smoking history, stage, Eastern Cooperative Oncology Group Performance Status (ECOG PS), lines of treatment, ICI drugs, brain metastasis, treatment type, and D-dimer levels. Kaplan-Meier analysis and Cox proportional hazards model were used for analyzing survival data, including progression-free survival (PFS, the time from initial ICI treatment to PD or death), overall survival (OS, the time between initial ICI treatment and death), and hazard ratio (HR). Follow-up of all patients was performed by searching electronic medical records and counseling telephone. The follow-up cut-off date was July 6, 2020.ResultsThis study included 277 advanced NSCLC patients. Among the enrolled patients, 23.1% were female, 64.6% had non-squamous cell lung cancer, and 79.4% were stage IV. Univariate and multivariate analysis showed that pretreatment high D-dimer levels were independently associated with shortened PFS and OS (P<0.01). Subgroup analysis confirmed that pretreatment high D-dimer levels were associated with poor prognosis in most subsets. After balancing baseline covariates between the high D-dimer group and normal D-dimer group, the results indicated that patients with pretreatment high D-dimer levels had significantly shorter PFS [median: 6.4 vs. 11.5 months; HR, 1.70; 95% confidence ratio (CI): 1.25-2.37; P<0.001] and OS (median: 12.7 vs. 30.4 months; HR, 2.29; 95% CI: 1.54-3.41; P<0.001) than those with pretreatment normal D-dimer levels.ConclusionsPretreatment plasma D-dimer could serve as a convenient prognostic biomarker for advanced NSCLC patients receiving ICI treatment. Patients with pretreatment high D-dimer levels may have poor PFS and OS.
| S-EPMC9641356 | biostudies-literature
Project description:Although sarcopenia has been reported to predict survival in cancer patients, its impact on patients who received immune checkpoint inhibitors (ICIs) has not been thoroughly investigated. This systematic review aimed to assess the long-term oncologic impact of sarcopenia on patients who received ICIs. A systematic review of studies indexed in the PubMed, Embase, and Cochrane databases, up to April 1, 2021, was conducted. Studies that reported hazard ratios (HRs) for overall survival (OS) and progression-free survival (PFS) based on sarcopenia in patients treated with ICIs were included. The inverse variance method was used with a random-effects model for data analysis. A total of 1284 patients from 14 studies were included. Among the patients who received ICIs, patients with sarcopenia had a significant increase in overall mortality compared to patients without sarcopenia in univariate analyses (HR = 1.66, 95% CI = 1.20-2.29, p = 0.002) and in adjusted HRs (HR = 1.55, 95% CI = 1.15-2.10, p = 0.004). The same results were obtained for PFS by both univariate analysis (HR = 1.75, 95% CI = 1.37-2.23, p < 0.001) and adjusted HRs (HR = 1.63, 95% CI 1.28-2.09, p < 0.001). Sarcopenia appears to be an effective biomarker for predicting long-term oncologic outcomes in patients receiving ICI therapy and hence plays an important role when making treatment decisions. However, the fundamental role of this association with survival should be further investigated in large cohorts and clinical trials.
| S-EPMC8622936 | biostudies-literature
Project description:With the widespread use of immune checkpoint inhibitors (ICIs), identifying predictive biomarkers is critical. Recently, serum fucosylated haptoglobin (Fuc-Hp) was thought to play an important role in tumour immunity in several types of cancer. Therefore, evaluating serum Fuc-Hp in the peripheral blood can potentially identify non-invasive predictive biomarkers for the clinical efficacy of ICIs. In this study, 31 patients with advanced renal cell carcinoma (RCC) treated with nivolumab were enrolled and defined as responders or non-responders according to RECIST criteria. Serum samples were collected before and 1 month after treatment initiation, and an ELISA assay was performed using Aleuria Aurantia Lectin (AAL) and 10-7G monoclonal antibodies that recognise Fuc-mature Hp (Fuc-mHp) and Fuc-pro Hp (Fuc-pHp), respectively. We first measured AAL-haptoglobin (Fuc-mHp) and total haptoglobin levels before nivolumab and found that neither value could predict the clinical response. Notably, serum 10-7G levels were significantly lower in the responder group (p = 0.035). We also confirmed the use of serum 10-7G levels for predicting progressive disease after nivolumab (area under the curve, 0.816). Accordingly, low 10-7G levels were significantly correlated with better progression-free survival (p = 0.041). In conclusion, serum Fuc-pHp analysis may identify patients with advanced RCC who benefit from ICIs.
| S-EPMC10567678 | biostudies-literature
Project description:Treatment with immune checkpoint inhibitors (ICIs) has considerably improved prognosis in multiple cancers. However, regardless of PD-L1 expression and TMB, better predictive biomarkers are required to identify ICI-responsive patients. We analyzed a pan-cancer cohort as the discovery cohort to identify the role of Max's giant associated protein (MGA) mutation in the outcome of ICI treatment in different types of cancers. A pooled lung adenocarcinoma (LUAD) cohort was considered as the validation cohort. Another two LUAD cohorts who received conventional treatment were included for prognostic analysis and mechanism exploration. In the discovery cohort, MGA mutation was a favorable survival biomarker for patients with LUAD than in those with other types of cancers. MGA mutation was positively correlated with the TMB score. The results of the validation cohort were consistent with those of the discovery cohort. Patients with MGA mutation in the TMB-low subgroup had longer survival. Two LUAD cohorts who received standard treatment showed that the MGA mutation was not a prognostic biomarker for standard treatment. Mechanically, we found that the co-mutant genes did not affect the prognostic role of MGA mutation. Gene-set enrichment analysis revealed that genes belonging to the immunodeficiency pathway were enriched in the MGA wild-type group in LUAD. Moreover, activated NK cells were more enriched in the MGA mutant LUAD group. In conclusion, our results demonstrated that MGA mutation was an independent predictive biomarker for ICI therapy. These results may provide a novel insight into identifying potential patients with LUAD for ICI therapy.
| S-EPMC8558674 | biostudies-literature
Project description:ObjectivesIt remains controversial whether sarcopenia has any significant impact on the efficacy of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) or immune checkpoint inhibitors (ICIs) in patients with advanced non-small cell lung cancer (NSCLC). Therefore, in this study, we aimed to assess the association between sarcopenia and clinical outcomes in patients with advanced NSCLC receiving EGFR-TKIs or ICIs as a first-line therapy.MethodsWe retrospectively enrolled 131 patients with advanced NSCLC treated with first-line EGFR-TKIs or ICIs between 1 March 2019 and 31 March 2021. To estimate sarcopenia, we calculated skeletal muscle index (SMI) as the ratio of skeletal muscle area (cm2) to height squared (m2). Associations between sarcopenia and overall survival (OS) and progression-free survival (PFS) were evaluated using the Kaplan-Meier method and log-rank tests, respectively. A Cox proportional hazards regression model was used to assess the factors associated with OS and PFS. The Student's t-test or Mann-Whitney U test was used to compare the SMI between patients with or without objective response and disease control. The chi-squared test was used to compare adverse events (AEs) between patients with and without sarcopenia.ResultsAmong the 131 patients, 35 (26.7%) were diagnosed with sarcopenia. Sarcopenia was an independent predictor of poor OS and PFS (p < 0.05) overall and in the EGFR-TKI- and ICI-treated cohorts. Among all patients, those with sarcopenia showed significantly shorter OS and PFS than those without sarcopenia (median OS and PFS: 13.0 vs. 26.0 months and 6.4 vs. 15.1 months; both p < 0.001). These associations were consistent across the subtypes of most clinical characteristics. Statistically significant differences between the objective response (OR) and non-OR groups were also observed in the mean SMI (OR group, 43.89 ± 7.55 vs. non-OR group, 38.84 ± 7.11 cm2/m2; p < 0.001). In addition, we observed similar results with disease control (DC) and non-DC groups (DC group, 42.46 ± 7.64 vs. non-DCR group, 33.74 ± 4.31 cm2/m2; p < 0.001). The AEs did not differ significantly between the sarcopenia and non-sarcopenia groups.ConclusionSarcopenia before treatment might be a significant predictor of poor clinical outcomes (shorter OS and PFS, fewer ORs, less DC) in patients with advanced NSCLC treated with EGFR-TKIs or ICIs as the first-line therapy.
| S-EPMC10031770 | biostudies-literature
Project description:BackgroundReal-world data enables evaluation of immune checkpoint inhibitor (ICI) use in advanced melanoma management. We examined characteristics and outcomes of ICI-treated patients with advanced melanoma and organ dysfunction (baseline and emergent).Materials and methodsThis retrospective observational study used electronic health records derived from a nationwide data set to examine advanced melanoma patients treated with first-line ICIs (2011-2018). Clinical characteristics, real-world time to treatment discontinuation (rwTTD), and overall survival (OS) were analyzed for patients with normal organ function and those with organ dysfunction prior to ICI initiation. Patients with emergent dysfunction in the 90 days following ICI initiation were identified, and potentially associated characteristics were explored.ResultsOf 2,407 patients included, 1,884 and 1,717 had evaluable renal and hepatic laboratory values, respectively. Patients with baseline renal dysfunction (2.4%) were older and more frequently male, and less frequently treated with ICI combinations, than patients with normal renal function. Patients with baseline hepatic dysfunction (2.8%) were similar to patients with normal hepatic function regarding demographics and treatments received. Patients with baseline organ dysfunction displayed shorter rwTTD and OS. Among patients with normal baseline organ function, 4.6% and 7.4% developed renal and hepatic dysfunction within 90 days of ICI initiation, respectively; this was associated with combination ICI treatment.ConclusionPatients with advanced melanoma and baseline organ dysfunction frequently receive ICI treatment but have poorer clinical outcomes than patients with normal organ function. Among patients with normal renal and hepatic function at ICI initiation, emergent organ dysfunction rates in this real-world cohort are similar to those reported in clinical trials.Implications for practiceReal-world data provide an opportunity to understand treatment patterns, toxicity, and clinical outcomes among patients treated outside of clinical trials. This study confirms that patients with advanced melanoma and baseline renal or hepatic dysfunction are being treated with ICI therapy more frequently as monotherapy than in combination therapy. For those real-world patients with normal baseline organ function, emergent renal and hepatic dysfunction are both more common in patients treated with combination versus ICI monotherapy.
| S-EPMC7648349 | biostudies-literature
Project description:BackgroundSeveral immune checkpoint inhibitors (ICIs) are approved for the treatment of advanced urothelial carcinoma (UC). There are limited biomarkers for ICI-treated patients with UC. We investigated the association between body composition and clinical outcomes in ICI-treated UC patients.Materials and methodsWe conducted a retrospective analysis of 70 ICI-treated patients with advanced UC at Winship Cancer Institute from 2015 to 2020. Baseline computed tomography images within 2 months of ICI initiation were collected at mid-L3 and muscle and fat compartments (subcutaneous, intermuscular, and visceral) were segmented using SliceOMatic v5.0 (TomoVision, Magog, Canada). A prognostic body composition risk score (high: 0-1, intermediate: 2-3, or low-risk: 4) was created based on the β coefficient from the multivariate Cox model (MVA) following best-subset variable selection. Our body composition risk score was skeletal muscle index (SMI) + 2 × attenuated skeletal muscle (SM) mean + visceral fat index (VFI). Concordance statistics (C-statistics) were used to quantify the discriminatory magnitude of the predictive model.ResultsMost patients (70%) were men and the majority received ICIs in the second- (46%) or third-line (21%) setting. High-risk patients had significantly shorter overall survival (OS; hazard ratio [HR], 6.72; p < .001), progression-free survival (HR, 5.82; p < .001), and lower chance of clinical benefit (odds ratio [OR], 0.02; p = .003) compared with the low-risk group in MVA. The C-statistics for our body composition risk group and myosteatosis analyses were higher than body mass index for all clinical outcomes.ConclusionBody composition variables such as SMI, SM mean, and VFI may be prognostic and predictive of clinical outcomes in ICI-treated patients with UC. Larger, prospective studies are warranted to validate this hypothesis-generating data.Implications for practiceThis study developed a prognostic body composition risk scoring system using radiographic biomarkers for patients with bladder cancer treated with immunotherapy. The study found that the high-risk patients had significantly worse clinical outcomes. Notably, the study's model was better at predicting outcomes than body mass index. Importantly, these results suggest that radiographic measures of body composition should be considered for inclusion in updated prognostic models for patients with urothelial carcinoma treated with immunotherapy. These findings are useful for practicing oncologists in the academic or community setting, particularly given that baseline imaging is routine for patients starting on treatment with immunotherapy.
| S-EPMC8649001 | biostudies-literature