Dataset Information

Tumor Characteristics Associated with Benefit from Pembrolizumab in Advanced Non-Small Cell Lung Cancer.

ABSTRACT:

Purpose

Several biomarkers have been individually associated with response to PD-1 blockade, including PD-L1 and tumor mutational burden (TMB) in non-small cell lung cancer (NSCLC), and CD8 cells in melanoma. We sought to examine the relationship between these distinct variables with response to PD-1 blockade and long-term benefit.

Experimental design

We assessed the association between baseline tumor characteristics (TMB, PD-L1, CD4, and CD8) and clinical features and outcome in 38 patients with advanced NSCLC treated with pembrolizumab (median follow-up of 4.5 years, range 3.8-5.5 years).

Results

PD-L1 expression and CD8 infiltration correlated with each other and each significantly associated with objective response rate (ORR) and progression-free survival (PFS). TMB was independent of PD-L1 and CD8 expression, and trended towards association with ORR and PFS. There was no association between CD4 infiltration and outcomes. Only PD-L1 expression was correlated with overall survival (OS). Among 5 patients with long-term survival >3 years with no additional systemic therapy, PD-L1 expression was the only discriminating feature. The increased predictive value for PFS and OS of composite biomarker inclusive of PD-L1, CD8, CD4, and TMB was limited.

Conclusions

In patients with NSCLC treated with PD-1 blockade with long-term follow up, TMB, PD-L1, and CD8 were each associated with benefit from PD-1 blockade. Pretreatment PD-L1 expression was correlated with T lymphocyte infiltration and OS, whereas models incorporating TMB and infiltrating CD4 and CD8 lymphocytes did not substantially add to the predictive value of PD-L1 alone for OS.

SUBMITTER: Hu-Lieskovan S

PROVIDER: S-EPMC6901027 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature

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Publications

Tumor Characteristics Associated with Benefit from Pembrolizumab in Advanced Non-Small Cell Lung Cancer.

Hu-Lieskovan Siwen S Lisberg Aaron A Zaretsky Jesse M JM Grogan Tristan R TR Rizvi Hira H Wells Daniel K DK Carroll James J Cummings Amy A Madrigal John J Jones Benjamin B Gukasyan Jacklin J Shintaku I Peter IP Slamon Dennis D Dubinett Steven S Goldman Jonathan W JW Elashoff David D Hellmann Matthew D MD Ribas Antoni A Garon Edward B EB

Clinical cancer research : an official journal of the American Association for Cancer Research 20190521 16

<h4>Purpose</h4>Several biomarkers have been individually associated with response to PD-1 blockade, including PD-L1 and tumor mutational burden (TMB) in non-small cell lung cancer (NSCLC), and CD8 cells in melanoma. We sought to examine the relationship between these distinct variables with response to PD-1 blockade and long-term benefit.<h4>Experimental design</h4>We assessed the association between baseline tumor characteristics (TMB, PD-L1, CD4, and CD8) and clinical features and outcome in ...[more]

PMID: 31113840

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Project description:BACKGROUNDThe anti-programmed cell death 1 (anti-PD-1) antibody pembrolizumab is clinically active against non-small cell lung cancer (NSCLC). In addition to T cells, human natural killer (NK) cells, reported to have the potential to prolong the survival of patients with advanced NSCLC, also express PD-1. This study aimed to investigate the safety and efficacy of pembrolizumab plus allogeneic NK cells in patients with previously treated advanced NSCLC.METHODSIn total, 109 enrolled patients with a programmed death ligand 1 (PD-L1) tumor proportion score (TPS) of 1% or higher were randomly allocated to group A (n = 55 patients given pembrolizumab plus NK cells) or group B (n = 54 patients given pembrolizumab alone). The patients received i.v. pembrolizumab (10 mg/kg) once every 3 weeks and continued treatment until the occurrence of tumor progression or unacceptable toxicity. The patients in group A continuously received 2 cycles of NK cell therapy as 1 course of treatment.RESULTSIn our study, patients in group A had longer survival than did patients in group B (median overall survival [OS]: 15.5 months vs. 13.3 months; median progression-free survival [PFS]: 6.5 months vs. 4.3 months; P < 0.05). In group A patients with a TPS of 50% or higher, the median OS and PFS was significantly longer. Moreover, the patients in group A treated with multiple courses of NK cell infusion had better OS (18.5 months) than did those who received a single course of NK cell infusion (13.5 months).CONCLUSIONPembrolizumab plus NK cell therapy yielded improved survival benefits in patients with previously treated PD-L1+ advanced NSCLC.TRIAL REGISTRATIONClinicalTrials.gov NCT02843204.FUNDINGThis work was supported by grants from the National Natural Science Foundation of China (NSFC) - Guangdong Joint Foundation of China (no. U1601225); the NSFC (no. 81671965); the Guangdong Provincial Key Laboratory Construction Project of China (no. 2017B030314034); and the Key Scientific and Technological Program of Guangzhou City (no. 201607020016).

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Project description:ObjectivePembrolizumab has become an integral first line therapeutic agent for non-small cell lung cancer (NSCLC), but its potential predictive role in clinical and molecular characteristics remains to be clarified. Accordingly, we performed a systematic review and meta-analysis to evaluate the clinical benefit of pembrolizumab in treatment of first line NSCLC and to select individuals with the greatest potential benefit from pembrolizumab therapy, in order to obtain a more accurate treatment of NSCLC in immunotherapy.MethodsMainstream oncology datasets and conferences were searched for randomized clinical trials (RCTs) published before August 2022. RCTs involved individuals with first line NSCLC treated with pembrolizumab monotherapy or in combination with chemotherapy. Two authors independently selected the studies, extracted data, and assessed the risk of bias. The basic characteristics of the included studies were recorded, along with 95 percent confidence intervals (CI) and hazard ratios (HR) for all patients and subgroups. The primary endpoint was overall survival (OS), and secondary endpoints was progression-free survival (PFS). Pooled treatment data were estimated using the inverse variance-weighted method.ResultsFive RCTs involving 2,877 individuals were included in the study. Pembrolizumab-based therapy significantly improved OS (HR 0.66; CI 95%, 0.55-0.79; p < 0.00001) and PFS (HR 0.60; CI 95%, 0.40-0.91; p = 0.02) compared with chemotherapy. OS was substantially enhanced in individuals aged < 65 years (HR 0.59; CI 95%, 0.42-0.82; p = 0.002), males (HR 0.74; CI 95%, 0.65-0.83; p < 0.00001), with a smoking history (HR 0.65; CI 95%, 0.52-0.82; p = 0.0003), with PD-L1 tumor proportion score (TPS) < 1% (HR 0.55; CI 95%, 0.41-0.73; p < 0.0001) and TPS ≥ 50% (HR 0.66; CI 95%, 0.56-0.76; p < 0.00001), but not in individuals aged ≥ 75 years (HR 0.82; CI 95%, 0.56-1.21; p = 0.32), females (HR 0.57; CI 95%, 0.31-1.06; p = 0.08), never smokers (HR 0.57; CI 95%, 0.18-1.80; p = 0.34), or with TPS 1-49% (HR 0.72; CI 95%, 0.52-1.01; p = 0.06). Pembrolizumab significantly prolonged OS in NSCLC patients, regardless of histology type (squamous or non-squamous NSCLC), performance status (PS) (0 or 1), and brain metastatic status (all p < 0.05). Subgroup analysis revealed that pembrolizumab combined with chemotherapy had more favorable HR values than pembrolizumab monotherapy in improving the OS of individuals with different clinical and molecular features.ConclusionPembrolizumab-based therapy is a valuable option for first line treating advanced or metastatic NSCLC. Age, sex, smoking history and PD-L1 expression status can be used to predict the clinical benefit of pembrolizumab. Cautiousness was needed when using pembrolizumab in NSCLC patients aged ≥ 75 years, females, never smokers, or in patients with TPS 1-49%. Furthermore, pembrolizumab in combination with chemotherapy may be a more effective treatment regimen.

Dataset Information

Tumor Characteristics Associated with Benefit from Pembrolizumab in Advanced Non-Small Cell Lung Cancer.

Purpose

Experimental design

Results

Conclusions

Publications

Tumor Characteristics Associated with Benefit from Pembrolizumab in Advanced Non-Small Cell Lung Cancer.

Similar Datasets

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