First-line Pembrolizumab Versus Pembrolizumab Plus Chemotherapy Versus Chemotherapy Alone in Non–small-cell Lung Cancer

A Systematic Review and Network Meta-analysis

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Abstract

Background: This study aimed to comprehensively review the available evidence regarding the efficacy of first-line pembrolizumab for advanced/metastatic non–small-cell lung cancer (NSCLC), and to compare pembrolizumab monotherapy versus pembrolizumab plus chemotherapy versus chemotherapy alone. Materials and Methods: A search of the PubMed, EMBASE, and Cochrane Library databases was performed in July 2018, and abstracts from the American Society of Clinical Oncology meetings (2015-2018) were reviewed. Summaries of the results were pooled using a random-effect model to determine the pooled hazard ratio (HR) for progression-free survival (PFS), overall survival (OS), and their 95% confidence intervals (CIs). A network meta-analysis was used to indirectly compare pembrolizumab monotherapy with pembrolizumab plus chemotherapy. Results: A total of 4 relevant phase III trials comprising 2754 patients were identified. Pembrolizumab (with or without chemotherapy) led to significant improvements in OS and PFS, irrespective of the programmed cell death ligand 1 (PD-L1) tumor proportion score (TPS). In particular, for the subgroup with PD-L1 TPS ≥ 50%, the HR of PFS was 0.49 (95% CI, 0.32-0.76; P = .001), and that of OS was 0.57 (95% CI, 0.45-0.73; P < .001). In terms of PFS, pembrolizumab plus chemotherapy was superior to pembrolizumab monotherapy with an HR of PFS 0.52 (95% CI, 0.27-0.99; P = .048) for the subgroup with PD-L1 TPS ≥ 50%. Conclusions: For patients with NSCLC with PD-L1 TPS ≥ 50%, pembrolizumab plus chemotherapy has a better PFS than pembrolizumab monotherapy in this meta-analysis. To confirm this finding, a prospective phase III trial that directly compares the treatments is warranted. Immunotherapy has revolutionized lung cancer management. Our study focused on the efficacy of first-line pembrolizumab for treatment of non–small-cell lung cancer by summarizing 4 phase III clinical trials. This analysis revealed that pembrolizumab in combination with chemotherapy exhibited better survival outcome than pembrolizumab monotherapy.

Original languageEnglish
Pages (from-to)331-338.e4
JournalClinical Lung Cancer
Volume20
Issue number5
DOIs
StatePublished - 1 Sep 2019

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Non-Small Cell Lung Carcinoma
Drug Therapy
Disease-Free Survival
Cell Death
Confidence Intervals
Ligands
Survival
pembrolizumab
Network Meta-Analysis
Neoplasms
Phase III Clinical Trials
Combination Drug Therapy
PubMed
Immunotherapy
Libraries
Meta-Analysis
Lung Neoplasms
Databases

Keywords

  • Immunotherapy
  • Meta-analysis
  • Network meta-analysis
  • Non-small cell lung cancer
  • Pembrolizumab

Cite this

@article{132e43017f174cfa9c3442a3e704fa57,
title = "First-line Pembrolizumab Versus Pembrolizumab Plus Chemotherapy Versus Chemotherapy Alone in Non–small-cell Lung Cancer: A Systematic Review and Network Meta-analysis",
abstract = "Background: This study aimed to comprehensively review the available evidence regarding the efficacy of first-line pembrolizumab for advanced/metastatic non–small-cell lung cancer (NSCLC), and to compare pembrolizumab monotherapy versus pembrolizumab plus chemotherapy versus chemotherapy alone. Materials and Methods: A search of the PubMed, EMBASE, and Cochrane Library databases was performed in July 2018, and abstracts from the American Society of Clinical Oncology meetings (2015-2018) were reviewed. Summaries of the results were pooled using a random-effect model to determine the pooled hazard ratio (HR) for progression-free survival (PFS), overall survival (OS), and their 95{\%} confidence intervals (CIs). A network meta-analysis was used to indirectly compare pembrolizumab monotherapy with pembrolizumab plus chemotherapy. Results: A total of 4 relevant phase III trials comprising 2754 patients were identified. Pembrolizumab (with or without chemotherapy) led to significant improvements in OS and PFS, irrespective of the programmed cell death ligand 1 (PD-L1) tumor proportion score (TPS). In particular, for the subgroup with PD-L1 TPS ≥ 50{\%}, the HR of PFS was 0.49 (95{\%} CI, 0.32-0.76; P = .001), and that of OS was 0.57 (95{\%} CI, 0.45-0.73; P < .001). In terms of PFS, pembrolizumab plus chemotherapy was superior to pembrolizumab monotherapy with an HR of PFS 0.52 (95{\%} CI, 0.27-0.99; P = .048) for the subgroup with PD-L1 TPS ≥ 50{\%}. Conclusions: For patients with NSCLC with PD-L1 TPS ≥ 50{\%}, pembrolizumab plus chemotherapy has a better PFS than pembrolizumab monotherapy in this meta-analysis. To confirm this finding, a prospective phase III trial that directly compares the treatments is warranted. Immunotherapy has revolutionized lung cancer management. Our study focused on the efficacy of first-line pembrolizumab for treatment of non–small-cell lung cancer by summarizing 4 phase III clinical trials. This analysis revealed that pembrolizumab in combination with chemotherapy exhibited better survival outcome than pembrolizumab monotherapy.",
keywords = "Immunotherapy, Meta-analysis, Network meta-analysis, Non-small cell lung cancer, Pembrolizumab",
author = "Ryul Kim and Bhumsuk Keam and Seokyung Hahn and Ock, {Chan Young} and Kim, {Mi So} and Kim, {Tae Min} and Dong-Wan Kim and Heo, {Dae Seog}",
year = "2019",
month = "9",
day = "1",
doi = "10.1016/j.cllc.2019.05.009",
language = "English",
volume = "20",
pages = "331--338.e4",
journal = "Clinical Lung Cancer",
issn = "1525-7304",
publisher = "Elsevier",
number = "5",

}

TY - JOUR

T1 - First-line Pembrolizumab Versus Pembrolizumab Plus Chemotherapy Versus Chemotherapy Alone in Non–small-cell Lung Cancer

T2 - A Systematic Review and Network Meta-analysis

AU - Kim, Ryul

AU - Keam, Bhumsuk

AU - Hahn, Seokyung

AU - Ock, Chan Young

AU - Kim, Mi So

AU - Kim, Tae Min

AU - Kim, Dong-Wan

AU - Heo, Dae Seog

PY - 2019/9/1

Y1 - 2019/9/1

N2 - Background: This study aimed to comprehensively review the available evidence regarding the efficacy of first-line pembrolizumab for advanced/metastatic non–small-cell lung cancer (NSCLC), and to compare pembrolizumab monotherapy versus pembrolizumab plus chemotherapy versus chemotherapy alone. Materials and Methods: A search of the PubMed, EMBASE, and Cochrane Library databases was performed in July 2018, and abstracts from the American Society of Clinical Oncology meetings (2015-2018) were reviewed. Summaries of the results were pooled using a random-effect model to determine the pooled hazard ratio (HR) for progression-free survival (PFS), overall survival (OS), and their 95% confidence intervals (CIs). A network meta-analysis was used to indirectly compare pembrolizumab monotherapy with pembrolizumab plus chemotherapy. Results: A total of 4 relevant phase III trials comprising 2754 patients were identified. Pembrolizumab (with or without chemotherapy) led to significant improvements in OS and PFS, irrespective of the programmed cell death ligand 1 (PD-L1) tumor proportion score (TPS). In particular, for the subgroup with PD-L1 TPS ≥ 50%, the HR of PFS was 0.49 (95% CI, 0.32-0.76; P = .001), and that of OS was 0.57 (95% CI, 0.45-0.73; P < .001). In terms of PFS, pembrolizumab plus chemotherapy was superior to pembrolizumab monotherapy with an HR of PFS 0.52 (95% CI, 0.27-0.99; P = .048) for the subgroup with PD-L1 TPS ≥ 50%. Conclusions: For patients with NSCLC with PD-L1 TPS ≥ 50%, pembrolizumab plus chemotherapy has a better PFS than pembrolizumab monotherapy in this meta-analysis. To confirm this finding, a prospective phase III trial that directly compares the treatments is warranted. Immunotherapy has revolutionized lung cancer management. Our study focused on the efficacy of first-line pembrolizumab for treatment of non–small-cell lung cancer by summarizing 4 phase III clinical trials. This analysis revealed that pembrolizumab in combination with chemotherapy exhibited better survival outcome than pembrolizumab monotherapy.

AB - Background: This study aimed to comprehensively review the available evidence regarding the efficacy of first-line pembrolizumab for advanced/metastatic non–small-cell lung cancer (NSCLC), and to compare pembrolizumab monotherapy versus pembrolizumab plus chemotherapy versus chemotherapy alone. Materials and Methods: A search of the PubMed, EMBASE, and Cochrane Library databases was performed in July 2018, and abstracts from the American Society of Clinical Oncology meetings (2015-2018) were reviewed. Summaries of the results were pooled using a random-effect model to determine the pooled hazard ratio (HR) for progression-free survival (PFS), overall survival (OS), and their 95% confidence intervals (CIs). A network meta-analysis was used to indirectly compare pembrolizumab monotherapy with pembrolizumab plus chemotherapy. Results: A total of 4 relevant phase III trials comprising 2754 patients were identified. Pembrolizumab (with or without chemotherapy) led to significant improvements in OS and PFS, irrespective of the programmed cell death ligand 1 (PD-L1) tumor proportion score (TPS). In particular, for the subgroup with PD-L1 TPS ≥ 50%, the HR of PFS was 0.49 (95% CI, 0.32-0.76; P = .001), and that of OS was 0.57 (95% CI, 0.45-0.73; P < .001). In terms of PFS, pembrolizumab plus chemotherapy was superior to pembrolizumab monotherapy with an HR of PFS 0.52 (95% CI, 0.27-0.99; P = .048) for the subgroup with PD-L1 TPS ≥ 50%. Conclusions: For patients with NSCLC with PD-L1 TPS ≥ 50%, pembrolizumab plus chemotherapy has a better PFS than pembrolizumab monotherapy in this meta-analysis. To confirm this finding, a prospective phase III trial that directly compares the treatments is warranted. Immunotherapy has revolutionized lung cancer management. Our study focused on the efficacy of first-line pembrolizumab for treatment of non–small-cell lung cancer by summarizing 4 phase III clinical trials. This analysis revealed that pembrolizumab in combination with chemotherapy exhibited better survival outcome than pembrolizumab monotherapy.

KW - Immunotherapy

KW - Meta-analysis

KW - Network meta-analysis

KW - Non-small cell lung cancer

KW - Pembrolizumab

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U2 - 10.1016/j.cllc.2019.05.009

DO - 10.1016/j.cllc.2019.05.009

M3 - Article

VL - 20

SP - 331-338.e4

JO - Clinical Lung Cancer

JF - Clinical Lung Cancer

SN - 1525-7304

IS - 5

ER -