Dataset Information

Association of the Lung Immune Prognostic Index With Immune Checkpoint Inhibitor Outcomes in Patients With Advanced Non-Small Cell Lung Cancer.

ABSTRACT: Importance:Derived neutrophils/(leukocytes minus neutrophils) ratio (dNLR) and lactate dehydrogenase (LDH) level have been correlated with immune checkpoint inhibitor (ICI) outcomes in patients with melanoma. Objective:To determine whether pretreatment dNLR and LDH are associated with resistance to ICIs in patients with advanced non-small cell lung cancer (NSCLC). Design, Setting, and Participants:Multicenter retrospective study with a test (n?=?161) and a validation set (n?=?305) treated with programmed death 1/programmed death ligand 1 (PD-1/PD-L1) inhibitors in 8 European centers, and a control cohort (n?=?162) treated with chemotherapy only. Complete blood cell counts, LDH, and albumin levels were measured before ICI treatment. A lung immune prognostic index (LIPI) based on dNLR greater than 3 and LDH greater than upper limit of normal (ULN) was developed, characterizing 3 groups (good, 0 factors; intermediate, 1 factor; poor, 2 factors). Main Outcomes and Measures:The primary end point was overall survival (OS). Secondary end points were progression-free survival (PFS) and disease control rate (DCR). Results:In the pooled ICI cohort (N?=?466), 301 patients (65%) were male, 422 (90%) were current or former smokers, and 401 (87%) had performance status of 1 or less; median age at diagnosis was 62 (range, 29-86) years; 270 (58%) had adenocarcinoma and 159 (34%) had squamous histologic subtype. Among 129 patients with PD-L1 data, 96 (74%) had PD-L1?of at least?1% by immunohistochemical analysis, and 33 (26%) had negative results. In the test cohort, median PFS and OS were 3 (95% CI, 2-4) and 10 (95% CI, 8-13) months, respectively. A dNLR greater than 3 and LDH greater than ULN were independently associated with OS (hazard ratio [HR] 2.22; 95% CI, 1.23-4.01 and HR, 2.51; 95% CI, 1.32-4.76, respectively). Median OS for poor, intermediate, and good LIPI was 3 months (95% CI, 1 month to not reached [NR]), 10 months (95% CI, 8 months to NR), and 34 months (95% CI, 17 months to NR), respectively, and median PFS was 2.0 (95% CI, 1.7-4.0), 3.7 (95% CI, 3.0-4.8), and 6.3 (95% CI, 5.0-8.0) months (both P?

SUBMITTER: Mezquita L

PROVIDER: S-EPMC5885829 | biostudies-other | 2018 Mar

REPOSITORIES: biostudies-other

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Association of the Lung Immune Prognostic Index With Immune Checkpoint Inhibitor Outcomes in Patients With Advanced Non-Small Cell Lung Cancer.

Mezquita Laura L Auclin Edouard E Ferrara Roberto R Charrier Melinda M Remon Jordi J Planchard David D Ponce Santiago S Ares Luis Paz LP Leroy Laura L Audigier-Valette Clarisse C Felip Enriqueta E Zerón-Medina Jorge J Garrido Pilar P Brosseau Solenn S Zalcman Gérard G Mazieres Julien J Caramela Caroline C Lahmar Jihene J Adam Julien J Chaput Nathalie N Soria Jean Charles JC Besse Benjamin B

JAMA oncology 20180301 3

<h4>Importance</h4>Derived neutrophils/(leukocytes minus neutrophils) ratio (dNLR) and lactate dehydrogenase (LDH) level have been correlated with immune checkpoint inhibitor (ICI) outcomes in patients with melanoma.<h4>Objective</h4>To determine whether pretreatment dNLR and LDH are associated with resistance to ICIs in patients with advanced non-small cell lung cancer (NSCLC).<h4>Design, setting, and participants</h4>Multicenter retrospective study with a test (n = 161) and a validation set (n ...[more]

PMID: 29327044

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Project description:ImportanceHigh body mass index (BMI) is independently associated with overall survival benefit from immune checkpoint inhibitor therapy in patients with melanoma, yet whether BMI is associated with outcomes in patients with advanced non-small cell lung cancer treated with atezolizumab remains unknown.ObjectiveTo examine whether BMI is associated with survival outcomes and adverse events in patients with non-small cell lung cancer (NSCLC) treated with atezolizumab.Design, setting, and participantsA pooled analysis of individual patient-level data from 4 international, multicenter clinical trials was performed. Two were single-arm phase 2 trials (BIRCH [data cutoff of May 28, 2015] and FIR [data cutoff of January 7, 2015]), and 2 were 2-arm randomized clinical trials (POPLAR [phase 2; data cutoff of May 8, 2015] and OAK [phase 3; data cutoff of July 7, 2016]). Patients with advanced NSCLC previously untreated or treated with at least 1 line of systemic therapy, with measurable disease and good organ function and without contraindications for chemotherapy or immune checkpoint inhibitor therapy, were included in these trials. Data analyses were performed from February 28, 2019, to September 30, 2019.InterventionsThe control group was treated with docetaxel once every 3 weeks until disease progression or unacceptable toxic effects occurred in POPLAR and OAK. The experimental group was treated with atezolizumab once every 3 weeks until disease progression or unacceptable toxic effects occurred in all available trials.Main outcomes and measuresAssociation between BMI and overall survival (OS), progression-free survival (PFS), and treatment-related adverse events. Intention-to-treat analysis was conducted.ResultsAdequate data were available for 2110 patients from a total pool of 2261 across 4 trials. Of those 2110, 1434 patients (median age, 64 years [range, 57-70 years]; 890 men [62%]) received atezolizumab and 676 patients (median age, 63 years[range, 57-69 years]; 419 men [62%]) received docetaxel. There was a linear association between increasing BMI and OS in patients treated with atezolizumab. Obesity (BMI ?30 [calculated as weight in kilograms divided by height in meters squared]) was associated with significantly improved OS in patients treated with atezolizumab, but not in those who received docetaxel after adjusting for confounding variables. The association between BMI and OS/PFS was the strongest in the high PD-L1 expression subgroup. Overall survival for patients with the highest category of PD-L1 expression (?50% of tumor cells or ?10% of tumor-infiltrating immune cells; n?=?436) had hazard ratios of 0.36 (95% CI, 0.21-0.62) for the group with obesity and 0.69 (95% CI, 0.48-0.98) for the group with overweight. Patients with the highest category of PD-L1 expression had PFS hazard ratios of 0.68 (95% CI, 0.49-0.94) for the group with obesity and 0.72 (95% CI, 0.56-0.92) for the group with overweight. Treatment-related adverse events were not associated with BMI.Conclusions and relevanceHigh BMI appears to be independently associated with improved survival with atezolizumab in patients with NSCLC, raising the possibility that baseline BMI should be considered as a stratification factor in future immune checkpoint inhibitor therapy trials.

Project description:BackgroundLung immune prognostic index (LIPI) status was recently developed to predict responses to immune checkpoint inhibitor (ICI) treatments. However, it is unclear whether LIPI is a prognostic index for both patients treated with ICI monotherapy and patients treated with ICIs combined with chemotherapy (ICIs CC).MethodsThis retrospective study established the patterns of LIPI in Chinese patients with advanced non-small cell lung cancer. Lung immune prognostic index based on the derived neutrophil-to-lymphocyte ratio greater than 3 and lactate dehydrogenase greater than the upper limit of normal was developed to characterize good, intermediate, or poor LIPI status. Associations between LIPI status and progression-free survival (PFS) and overall survival (OS) were analyzed. Kaplan-Meier curves and Cox proportional hazards models were used to determine survival differences.ResultsThree hundred thirty patients were included in this study. Of these patients, 216 received ICI monotherapy and 114 received ICIs CC. A good LIPI status was associated with better PFS (6.1 months vs. 2.3 months vs. 2.1 months, P = 0.023) and OS (24.2 months vs. 14.5 months vs. 9.3 months, P < 0.001) in ICI monotherapy compared to intermediate or poor LIPI status. No differences in PFS (17.9 vs. 9.9 months vs. 7.6 months, P = 0.355, respectively) and OS (P = 0.346) were observed in patients who received ICIs CC. Moreover, we found that patients who had an improved LIPI status compared with the baseline value had a longer PFS with ICI monotherapy and LIPI intermediate status (8.4 months vs. 2.1 months vs. 1.4 months, P < 0.001). However, in patients treated with ICIs CC, these dynamic changes were not observed (P = 0.444).ConclusionsLung immune prognostic index status and dynamic changes in LIPI could be prognostic markers of treatment response to ICI monotherapy, but not to ICIs CC. In particular, good LIPI status was associated with a better clinical outcome compared with intermediate and poor LIPI status in ICI monotherapy treatment.

Project description:BackgroundThe advent of immune checkpoint inhibitors (ICIs) therapy has resulted in significant survival benefits in patients with non-small-cell lung cancer (NSCLC) without increasing toxicity. However, the utilisation of immunotherapy for small-cell lung cancer (SCLC) remains unclear, with a scarcity of systematic comparisons of therapeutic effects and safety of immunotherapy in these two major lung cancer subtypes. Herein, we aimed to provide a comprehensive landscape of immunotherapy and systematically review its specific efficacy and safety in advanced lung cancer, accounting for histological types.MethodsWe identified studies assessing immunotherapy for lung cancer with predefined endpoints, including overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and treatment-related adverse events (TRAE), from PubMed, Embase, Medline, and Cochrane library. A random-effects or fixed-effect model was adopted according to different settings.ResultsOverall, 38 trials with 20,173 patients with lung cancer were included in this study. ICI therapy resulted in a significantly prolonged survival in both patients with NSCLC and SCLC when compared with chemotherapy (hazard ratio [HR] = 0.74; 95% confidence interval [CI], 0.70-0.79] and [HR = 0.82; 95% CI, 0.75-0.90], respectively). The magnitude of disease control and survival benefits appeared superior with ICI plus standard of care (SOC) when compared with SOC alone. OS and PFS advantages were observed only when immunotherapy was employed as the first-line treatment in patients with SCLC.ConclusionICI therapy is a promising therapeutic option in patients with NSCLC and SCLC. ICI plus SOC can be recommended as the optimal first-line treatment for patients with SCLC, and double-target ICIs combined with SOC are recommended in patients with NSCLC as both the first and subsequent lines of treatment. Additionally, non-first-line immunotherapy is not recommended in patients with SCLC.

Dataset Information

Association of the Lung Immune Prognostic Index With Immune Checkpoint Inhibitor Outcomes in Patients With Advanced Non-Small Cell Lung Cancer.

Publications

Association of the Lung Immune Prognostic Index With Immune Checkpoint Inhibitor Outcomes in Patients With Advanced Non-Small Cell Lung Cancer.

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