Results of an Italian CORE-IMMUNO study: Safety and clinical-related biomarkers as predictors of immunotherapy (IT) benefit in real-world treatment of various advanced tumors (ATs).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e14156-e14156 ◽  
Author(s):  
Cristina Masini ◽  
Annalisa Berselli ◽  
Alessandra Romagnani ◽  
Candida Bonelli ◽  
Emanuela Fantinel ◽  
...  
Keyword(s):  
Kidney Cancer ◽  
Real World ◽  
Cox Regression ◽  
Checkpoint Inhibitors ◽  
Study Data ◽  
World Population ◽  
Head Neck Cancer ◽  
Neutrophil Lymphocyte Ratio ◽  
Clinical Benefits ◽  
Head Neck

e14156 Background: Checkpoint inhibitors in cancer therapy have shown survival benefits in the treatment of several ATs. However, the risk of serious side effects seems greater in certain types of tumors presenting reduced compliance with therapy. The aim of this study is to evaluate the safety profile and clinical benefits of IT, as appraised using clinically related biomarkers of pts outside clinical trials. Methods: In this retrospective study, data were evaluated on pts in the Reggio Emilia Provincial Oncology Network who were treated for ATs using Nivolumab, Pembrolizumab and Ipilimumab monotherapy in clinical practice. The pts included in the study had received at least 1 dose of IT by June 2018. LDH and neutrophil–lymphocyte ratio (NLR) were collected at baseline, antibiotic therapy (ATB) was considered during IT, and immunorelated adverse events (irAEs) were assessed with CTCAE v.4.1. Results: A total of 169 pts were examined: 78 with NSCLC, 57 with melanoma, 29 with kidney cancer, 3 with head-neck cancer and 2 with colorectal cancer. 123 pts (73%) were treated with Nivolumab, 36 (21%) with Pembrolizumab and 10 (6%) with Ipilimumab. Overall, 62 pts (37%) experienced irAES of any degree: 17/29 (59%) pts with kidney cancer presented irAES, while only 35% (20/57) and 31% (24/78) of pts with melanoma and lung cancer did, respectively. A total of 27/62 (43%) pts delayed IT due to toxicity, but only 7/62 (11%) pts discontinued treatment due to irAEs. Statistically significant increases in PFS (11 vs. 5 months, p = 0.002) and OS (19.9 vs. 8.7 months, p = 0.002) were found between pts who experienced irAEs and those who did not. As previously demonstrated in other groups of pts, in the Cox regression performed for OS, a baseline value of LDH≥1.5xULN and median NLR ≥2.93 correlates with poor prognosis. Unlike what is already known, the use of ATB during IT (35% of pts) correlates with increased survival (HR 0.59; IC95% 0.37-0.94, p = 0.028). Conclusions: These data confirm the tolerability of IT in an unselected real-world population. In particular, the development of irAEs could be considered a positive predictor of outcome, but with a different incidence among MTS.

Biomarker to cost-effectively harness the technical prowess of palliative radiation: Neutrophil lymphocyte ratio (NLR) and overall survival following palliative radiotherapy in an unselected real-world population of all tumor sites.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 10111-10111
Author(s):  
Santhanam Sundar ◽  
James Price ◽  
Kirsty Clarke ◽  
Thomas Wolfe ◽  
D Thurairasa ◽  
...  
Keyword(s):  
Overall Survival ◽  
Real World ◽  
Cox Regression ◽  
Palliative Radiotherapy ◽  
Standard Of Care ◽  
University Hospital ◽  
World Population ◽  
Single Fraction ◽  
Neutrophil Lymphocyte Ratio ◽  
Lymphocyte Ratio

10111 Background: Single fraction radiotherapy (RT) is standard of care for palliation of pain from bone metastases (ASTRO IJROBP 2011 79:965). But costly, complex, multi-fraction RT is quite often used for palliation of symptoms from various organs. Health care costs are burgeoning (ASCO JCO 2012 30: 1715). Costs can be constrained by judiciously reducing use of unnecessary multi-fraction RT in pts with limited life expectancy. But radiation oncologists’ ability to predict survival is inaccurate. (Chow IJROBP 2005 61:870). Hence we assessed clinical utility of Neutrophil Lymphocyte ratio (NLR) - a routinely available biomarker. Methods: 233 patients (pts) undergoing palliative RT over a 3 month at Nottingham University Hospital. Predominant Tumour SITES: Lung 28% Breast 13% Prostate 13% Colorectal 9% Gastro-Oesophageal 5% Myeloma 5% Bladder 5%. Predominant HISTOLOGY: Adenocarcinoma 61% Squamous Cell 14%. NLR available for 158 pts. Results: A NLR of 4.5 was highly predictive of 90-day mortality & overall survival in an unselected real world population. (Table). No survival benefit seen for multi-fraction RT over single fraction RT across all tumour sites. On survival analysis by Cox regression, increased NLR was significant with a hazard ratio of 2.2 (95% CI 1.3 to 3.7) whereas total radiation dose, use of multiple fractions , age, serum haemoglobin, serum albumin & histology were not significant. Conclusions: In palliative care of advanced cancer, for pts with high NLR (>4.5), Single fraction RT should be the standard of care for palliation of symptoms. [Table: see text]

Response to checkpoint inhibitors (CPI) in sarcomatoid renal cell carcinoma (sRCC).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e17095-e17095
Author(s):  
Iris Yeong- Fung Sheng ◽  
Wei Wei ◽  
Kunal Desai ◽  
Kimberly D. Allman ◽  
Allison Martin ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Real World ◽  
Systemic Therapy ◽  
Checkpoint Inhibitors ◽  
Cleveland Clinic ◽  
Clinical Trial Data ◽  
Trial Data ◽  
Rank Test ◽  
World Population ◽  
Related Factors

e17095 Background: sRCC have a generally poor prognosis though recent clinical trial data suggest improved outcomes with CPI. We present a real-world experience of metastatic sRCC patients (pts) treated with a variety of CPI. Methods: Pts with sRCC treated with CPI Cleveland Clinic from 1/1/2015 to 12/31/2019 were identified. Overall survival (OS) was estimated using Kaplan-Meier and compared by log rank test. Results: Of 28 eligible pts identified with sRCC, median age 58, 82% Caucasian, all KPS score > 80%, 86% had IMDC intermediate/poor risk disease, 75% were clear cell, and 71% had prior nephrectomy. 46.4% had prior non-CPI systemic therapy. CPI therapy in this cohort included: 46% nivolumab monotherapy, 18% axitinib/pembrolizumab, 21% ipilimumab/nivolumab, 4% atezolizumab/bevacizumab, 7% atezolizumab, 4% carboplatin/pemetrexed/pembrolizumab. At a median follow up of 13.6 months (range 6.5-31.4), ORR was 36% (4% CR, 32% PR) and median OS was 13.8 months (95% CI: 9.23-NA). Median time to response was 3.2 months (range 2.4-13.1) and median duration of response was 8.1 months (range 0-25.5). Ten of the 13 patients started subsequent therapy due to progression. At the time of analysis, 39% were still alive and 25% of patients were still on initial I/O therapy (7+ -30+ months). There were no clear correlations between specific disease-related factors (including IMDC risk, time-to treatment of > or < 1 year, or prior systemic therapy) and response (all were p > 0.05). Conclusions: ORR and CR rates were lower in this real-world population of metastatic sRCC pts compared to clinical trial data, which should be a result of various CPI treatments and lines of treatment. However, these data highlight the heterogeneity of sRCC in general and need for additional investigations into impact of percentage of sarcomatoid features, genomic analyses, line of therapy, and CPI choice to optimize outcomes in sRCC pts.

scholarly journals Hospitalization and Mortality in Patients With Heart Failure Treated With Sacubitril/Valsartan vs. Enalapril: A Real-World, Population-Based Study

2021 ◽  
Vol 7 ◽  
Author(s):  
Swathi Pathadka ◽  
Vincent K. C. Yan ◽  
Xue Li ◽  
Gary Tse ◽  
Eric Y. F. Wan ◽  
...  
Keyword(s):  
Heart Failure ◽  
Cardiovascular Mortality ◽  
Real World ◽  
Cox Regression ◽  
Population Based ◽  
World Population ◽  
Composite Outcome ◽  
Patients With Heart Failure ◽  
All Cause Mortality ◽  
Primary Composite Outcome

Background: The effect of sacubitril/valsartan on survival and hospitalization risk in older patients with heart failure has not been explored. We aimed to investigate the risk of hospitalization and mortality with the use of sacubitril/valsartan vs. enalapril in patients with heart failure.Methods: This was a population-based cohort study using the Hong Kong-wide electronic healthcare database. Patients diagnosed with heart failure and newly prescribed sacubitril/valsartan or enalapril between July 2016 and June 2019 were included. The risk of primary composite outcome of cardiovascular mortality or heart failure-related hospitalization, all-cause hospitalization, heart failure-related hospitalization, cardiovascular mortality and all-cause mortality were compared using Cox regression with inverse probability treatment weighting. Additional analysis was conducted by age stratification.Results: Of the 44,503 patients who received sacubitril/valsartan or enalapril, 3,237 new users (sacubitril/valsartan, n = 1,056; enalapril, n = 2,181) with a diagnosis of heart failure were identified. Compared with enalapril, sacubitril/valsartan users were associated with a lower risk of primary composite outcome [hazard ratio (HR) 0.58; 95% confidence interval (CI), 0.45–0.75], heart failure-related hospitalization (HR 0.59; 95% CI, 0.45–0.77), all-cause mortality (HR 0.51; 95% CI, 0.36–0.74) and borderline non-significant reductions in all-cause hospitalization (HR 0.85; 95% CI, 0.70–1.04) and cardiovascular mortality (HR 0.63; 95% CI, 0.39–1.02). The treatment effect of sacubitril/valsartan remains unaltered in the patient subgroup age ≥ 65 years (73%).Conclusions: In real-world settings, sacubitril/valsartan was associated with improved survival and reduced heart failure-related hospitalization compared to enalapril in Asian patients with heart failure. The effectiveness remains consistent in the older population.

T-cell inflamed gene expression to predict prognosis and response to immune checkpoint inhibitors.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e15264-e15264
Author(s):  
Yao Yu ◽  
Jingjiao Ma ◽  
Jie Chen ◽  
Ning He ◽  
Xiaohong Xu ◽  
...  
Keyword(s):  
Gene Expression ◽  
T Cell ◽  
Real World ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Cox Regression ◽  
Checkpoint Inhibitors ◽  
Objective Response ◽  
Small Sample ◽  
Youden Index

e15264 Background: To prove that T-cell-inflamed gene-expression profile (GEP) can predict prognosis and response to immune checkpoint inhibitors (ICIs) in the real-world study. Methods: 36 patients admitted from January 2018 to December 2018 were enrolled, including 15 patients with advanced NSCLC, 12 with advanced bladder cancer and 9 with advanced liver cancer. All patients were treated with nivolumab or pembrolizumab and provided informed written consent for analysis. Tumor total RNA was isolated from pretreatment FFPE samples and RNA-seq was performed on the Illumina NovaSeq 6000 system. GEP was calculated as a weighted sum of normalized expression values for 18 genes, as described in the article written by Ayer M, et al. in 2017. The data cutoff date was July 30, 2019. Primary end points were objective response rate (ORR) and disease control rate (DCR). Secondary end point was progression-free survival (PFS) assessed per RECIST v1.1. 95% CIs and P values for ORR and DCR were evaluated by the binomial exact method. Correlation between GEP and ORR, DCR and PFS was assessed by Wilcoxon rank sum test and Cox regression model, respectively. Survival curves were estimated by Kaplan-Meier methods. Cut-off value of GEP was confirmed by the Youden Index. The comparisons of DCR and PFS were performed by Fisher’s exact test and log-rank test, respectively. Results: ORR was 30.6% (95% CI, 16.3%-48.1%) and DCR was 50.0% (95% CI, 32.9%-67.1%). Median PFS was 3.9 months (95% CI, 0.8-NR). We found that GEP was higher in patients who achieved DCR and had longer PFS. And then GEP was significantly associated with DCR (p = 0.019) and PFS (p = 0.005), but not significantly with ORR (p = 0.42). Based on Youden Index, cut-off value of GEP was confirmed as -0.368, with 94.4% of sensitivity and 66.7% of specificity. According to cut-off value, 23 patients were evaluated as GEP-H. GEP-H group had higher DCR and longer PFS (DCR: 73.9% vs 7.69%, p = 0.0003; mPFS: 7.0m vs 2.1m, p = 0.00049). Conclusions: GEP can predict prognosis and response to ICIs in multiple cancers in our real-world study. Interpretation of these data may be limited by small sample sizes. Further studies are being conducted.

Gastric inflammatory prognostic index (GIPI) to predict efficacy of PD-1/PD-L1 immune checkpoint inhibitors in metastatic gastroesophageal junction (GOJ)/gastric cancer (GC) patients.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 4530-4530
Author(s):  
Cristina Morelli ◽  
Vincenzo Formica ◽  
Anna Patrikidou ◽  
Carmen Murias ◽  
Sabeeh-Ur-Rehman Butt ◽  
...  
Keyword(s):  
Prognostic Value ◽  
Mononuclear Cells ◽  
Cox Regression ◽  
Checkpoint Inhibitors ◽  
Gastroesophageal Junction ◽  
Prognostic Index ◽  
Second Line ◽  
Continuous Variables ◽  
Neutrophil Lymphocyte Ratio ◽  
Lymphocyte Ratio

4530 Background: ICIs demonstrated improved overall survival (OS) in heavily pre-treated mGOJ/GC pts. Pts selection exclusively based on PD-L1 tissue expression appears to be suboptimal, despite data from subgroup analyses of KEYNOTE trials. Strong rationale suggests a potential predictive role of inflammatory biomarkers in ICIs treated mGOJ/GC pts. Methods: Ten systemic inflammatory markers [platelets, monocytes, neutrophil/lymphocyte ratio (NLR), platelets-lymphocyte ratio, lymphocytes, sum of mononuclear cells, albumin, lactate dehydrogenase, c-reactive protein (CRP) and serum globulin] were retrospectively analyzed at baseline in 57 mGOJ/GC pts with unknown PD-L1 status treated in second-line with ICIs, and correlated with OS. Least Absolute Shrinkage and Selection Operator (LASSO) method was used to select variables (preliminarily subject to optimal coding using HR smoothed curves for OS) with the highest prognostic value. Selected variables were then analyzed in a multivariate Cox Regression Model and used to build a GIPI nomogram. Results: NLR and CRP taken as continuous variables and albumin categorized as < vs > 30 g/dL were found as the most meaningful independent predictors of OS and used to build the GIPI nomogram. Nomogram-based lowest (l), mid-low, mid-high and highest (h) risk quartiles were associated with median(m)OS of 14.9, 7.1, 5.6 and 2.1 months (mos), respectively [HR of l vs h 4.94, p 0.0002]. By optimally dichotomizing CRP and NLR, pts with one or more of the following risk factors: NLR >6, CRP >15 mg/L, albumin <30 g/dL (n: 29) had a mOS of 3.9 mos vs 14.2 mos of pts with no risk factor (n: 28) (HR 2.48, p 0.001). Conclusions: GIPI, combining NLR, CRP and Albumin, is the first inflammatory index with a significant prognostic value in mOGJ/GC pts receiving second-line ICIs. Its implementation in correlation with PD-L1 expression in the present cohort is ongoing. GIPI merits validation in independent cohorts and prospective clinical trials.

scholarly journals Real-world comparative effectiveness of second-line ipilimumab for metastatic melanoma: a population-based cohort study in Ontario, Canada

2020 ◽  
Author(s):  
Wei Fang Dai ◽  
Jaclyn Beca ◽  
Ruth Croxford ◽  
Wanrudee Isaranawatchai ◽  
Ines B. Menjak ◽  
...  
Keyword(s):  
Real World ◽  
Comparative Effectiveness ◽  
Cox Regression ◽  
Population Based ◽  
Administrative Databases ◽  
Routine Practice ◽  
World Population ◽  
Second Line ◽  
Drug Databases ◽  
Historical Controls

Abstract Background For novel cancer treatments, effectiveness in clinical practice is not always aligned with clinical efficacy results. As such it is important to understand a treatment’s real-world effectiveness. We examined real-world population-based comparative effectiveness of second-line ipilimumab versus non-ipilimumab treatments (chemotherapy or targeted treatments). Methods We used a cohort of melanoma patients receiving systemic treatment for advanced disease since April 2005 from Ontario, Canada. Patients were identified from provincial drug databases and the Ontario Cancer Registry who received second-line ipilimumab from 2012 to 2015 (treated) or second-line non-ipilimumab treatment prior to 2012 (historical controls). Historical controls were chosen, to permit the most direct comparison to pivotal trial findings. The cohort was linked to administrative databases to identify baseline characteristics and outcomes. Kaplan-Meier curves and multivariable Cox regression models were used to assess overall survival (OS). Observed potential confounders were adjusted for using inverse probability of treatment weighting. Results We identified 329 patients with MM who had received second-line treatments (189 treated; 140 controls). Patients receiving second-line ipilimumab were older (61.7 years vs 55.2 years) compared to historical controls. Median OS were 6.9 (95% CI: 5.4-8.3) and 4.95 (4.3-6.0) months for ipilimumab and controls, respectively. The crude 1-year, 2-year, and 3-year OS probabilities were 34.3% (27%-41%), 20.6% (15%-27%), and 15.2% (9.6%-21%) for ipilimumab and 17.1% (11%-23%), 7.1% (2.9%-11%), and 4.7% (1.2%-8.2%) for controls. Ipilimumab was associated with improved OS (IPTW HR=0.62; 95% CI: 0.49-0.78; p <0.0001). Conclusions This real-world analysis suggests second-line ipilimumab is associated with an improvement in OS for MM patients in routine practice.

Predictive value of fibroblast growth factor receptor (FGFR) alterations on anti-PD-(L)1 treatment outcomes in patients (Pts) with advanced urothelial cancer (UC): Pooled analysis of real-world data.

2020 ◽  
Vol 38 (6_suppl) ◽  
pp. 493-493
Author(s):  
William Y. Kim ◽  
Tracy L. Rose ◽  
Florian Roghmann ◽  
Markus Eckstein ◽  
Jonas Jarczyk ◽  
...  
Keyword(s):  
Treatment Outcomes ◽  
Real World ◽  
Predictive Value ◽  
Cox Regression ◽  
Multivariate Analyses ◽  
Checkpoint Inhibitors ◽  
Small Sample ◽  
Smoking History ◽  
Second Line ◽  
First Line

493 Background: The tumor microenvironment in UC harboring FGFR gene alterations is characterized by decreased T-cell infiltration and low immune marker expression, potentially implicating suboptimal response to immune checkpoint inhibitors. The association between FGFR gene mutations/fusions and anti-PD-(L)1 treatment outcomes in advanced UC was assessed using real-world pt data. Methods: A pooled dataset of matched clinical and genomic data for advanced UC pts treated with anti-PD-(L)1 in any line from the Bladder Cancer Research Initiative for Drug Targets in Germany (BRIDGE) Consortium and UNC-CH was assessed. FGFR status was defined by a prespecified panel of FGFR2/3 mutations and fusions. Overall survival (OS) was analyzed using Kaplan-Meier estimates and Cox proportional hazards models. Multivariate analyses were performed using potential prognostic covariates (sex, age, baseline tumor stage, urothelial histology, smoking history, primary tumor location, and ECOG) in a Cox regression model for OS to assess their impact on the effect of FGFR alterations. Results: Median OS for FGFR+ pts (n=28) who received any line of anti-PD-(L)1 therapy was 9.5 mo vs 7.5 mo for FGFR− pts (n=139) (HR: 1.03, 95% CI: 0.60-1.76, p=0.93). Median OS for pts treated with first-line anti-PD-(L)1 was 5.42 mo in FGFR+ pts (n=10) and was not reached for FGFR− pts (n=31) (HR: 2.06, 95% CI: 0.68-6.24, p=0.19); median OS in second-line anti-PD-(L)1 was 6.5 mo (FGFR+; n=14) vs 5.7 mo (FGFR−; n=86) (HR: 0.89, 95% CI: 0.44-1.81, p=0.74). The multivariate analyses showed a significant trend of poorer OS in FGFR+ pts with first-line anti-PD-(L)1 (HR: 10.42, 95% CI: 1.45-74.97, p=0.02); wide CI may be attributed to small sample size for some categories in several covariates. Conclusions: Treatment with first-line anti-PD-(L)1 in FGFR+ pts may be associated with poorer OS outcomes in FGFR+ pts; however, this trend was not observed in FGFR+ pts treated with any line and second-line anti-PD-(L)1. Investigation of the predictive value of FGFR alterations to immunotherapy outcomes in larger real-world pt datasets is warranted.

scholarly journals Real-world comparative effectiveness of second-line ipilimumab for metastatic melanoma: a population-based cohort study in Ontario, Canada

2020 ◽  
Author(s):  
Wei Fang Dai ◽  
Jaclyn Beca ◽  
Ruth Croxford ◽  
Wanrudee Isaranawatchai ◽  
Ines B. Menjak ◽  
...  
Keyword(s):  
Real World ◽  
Comparative Effectiveness ◽  
Cox Regression ◽  
Population Based ◽  
Administrative Databases ◽  
Routine Practice ◽  
World Population ◽  
Second Line ◽  
Drug Databases ◽  
Historical Controls

Abstract Background For novel cancer treatments, effectiveness in clinical practice is not always aligned with clinical efficacy results. As such it is important to understand a treatment’s real-world effectiveness. We examined real-world population-based comparative effectiveness of second-line ipilimumab versus non-ipilimumab treatments (chemotherapy or targeted treatments). Methods We used a cohort of melanoma patients receiving systemic treatment for advanced disease since April 2005 from Ontario, Canada. Patients were identified from provincial drug databases and the Ontario Cancer Registry who received second-line ipilimumab from 2012 to 2015 (treated) or second-line non-ipilimumab treatment prior to 2012 (historical controls). Historical controls were chosen, to permit the most direct comparison to pivotal trial findings. The cohort was linked to administrative databases to identify baseline characteristics and outcomes. Kaplan-Meier curves and multivariable Cox regression models were used to assess overall survival (OS). Observed potential confounders were adjusted for using inverse probability of treatment weighting (IPTW). Results We identified 329 patients with MM who had received second-line treatments (189 treated; 140 controls). Patients receiving second-line ipilimumab were older (61.7 years vs 55.2 years) compared to historical controls. Median OS were 6.9 (95% CI: 5.4-8.3) and 4.95 (4.3-6.0) months for ipilimumab and controls, respectively. The crude 1-year, 2-year, and 3-year OS probabilities were 34.3% (27%-41%), 20.6% (15%-27%), and 15.2% (9.6%-21%) for ipilimumab and 17.1% (11%-23%), 7.1% (2.9%-11%), and 4.7% (1.2%-8.2%) for controls. Ipilimumab was associated with improved OS (IPTW HR=0.62; 95% CI: 0.49-0.78; p <0.0001). Conclusions This real-world analysis suggests second-line ipilimumab is associated with an improvement in OS for MM patients in routine practice.

Gastric Immune Prognostic Index (GIPI) in metastatic (m) gastro-oesophageal junction (GOJ)/gastric cancer (GC) patients (pts) treated with PD-1/PD-L1 immune checkpoint inhibitors (ICIs).

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 417-417 ◽  
Author(s):  
Cristina Morelli ◽  
Vincenzo Formica ◽  
Anna Patrikidou ◽  
Carmen Murrias ◽  
Sabeeh Butt ◽  
...  
Keyword(s):  
Mononuclear Cells ◽  
Cox Regression ◽  
Checkpoint Inhibitors ◽  
Prognostic Index ◽  
Tissue Expression ◽  
Second Line ◽  
Continuous Variables ◽  
Serum Globulin ◽  
Neutrophil Lymphocyte Ratio ◽  
Lymphocyte Ratio

417 Background: ICIs demonstrated improved overall survival (OS) in heavily pre-treated mGOJ/GC pts. Pts selection exclusively based on PD-L1 tissue expression appears to be suboptimal, despite data from subgroup analyses of KEYNOTE trials. Strong rationale suggests a potential predictive role of inflammatory biomarkers in ICIs treated mGOJ/GC pts. Methods: 11 systemic inflammatory markers [platelets, monocytes, neutrophil/lymphocyte ratio (NLR), platelets-lymphocyte ratio, lymphocytes, sum of mononuclear cells, albumin, lactate dehydrogenase, alkaline phosphatase (ALP), c-reactive protein (CRP) and serum globulin] were retrospectively analyzed at baseline in 57 mGOJ/GC pts with unknown PD-L1 status treated in second-line with ICIs, and correlated with OS. Least Absolute Shrinkage and Selection Operator (LASSO) method was used to select variables (preliminarily subject to optimal coding using HR smoothed curves for OS) with the highest prognostic value.Selected variables were then analysed in a multivariate Cox Regression Model and used to build a GIPI nomogram. Results: NLR and CRP taken as continuous variables and ALP categorized as < vs > 150 IU/L were found as the most meaningful independent predictors of OS [(HR 1.30 (95%CI 1.02-1.65), 2.00 (95%CI 1.09-3.66), 2.82 (95%CI 1.29-6.20) and p values 0.04, 0.01, 0.02, respectively)] and used to build the GIPI nomogram. Nomogram-based lowest(l), mid and highest(h) risk tertiles were associated with median(m)OS of 14.5,10.6 and 2.4 months(mos), respectively [HR of l vs h 0.26 (95%CI 0.12-0.53), p 0.0002]. By optimally dichotomizing CRP and NLR, pts with one or more of the following risk factors: NLR > 6, CRP > 15 mg/L, ALP < 150 IU/L (n: 31) had a mOS of 3.9mos vs 14.5mos of pts with no risk factor (n: 26) (HR 2.72, p 0.0005). Conclusions: GIPI, combining NLR, CRP and ALP, is the first inflammatory index with a significant prognostic value in mOGJ/GC pts receiving second line ICIs. Its implementation with analysis of PD-L1 expression in the present cohort is ongoing. GIPI merits validation in external cohorts and prospective clinical trials.

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