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Advances in Therapy

, Volume 35, Issue 7, pp 1035–1048 | Cite as

Comparative Efficacy of Treatments for Previously Treated Advanced or Metastatic Non-Small-Cell Lung Cancer: A Network Meta-Analysis

  • Junlong LiEmail author
  • Medha Sasane
  • Jing Zhao
  • Viviana Garcia Horton
  • Pingkuan Zhang
  • Marie Louise Ricculli
  • Zheng-Yi Zhou
  • James Signorovitch
Original Research

Abstract

Introduction

Due to the rarity of BRAF V600E mutation, no randomized study has compared the combination targeted therapy dabrafenib + trametinib with other second-line treatments for advanced or metastatic non-small-cell lung cancer (NSCLC). A network meta-analysis (NMA) was conducted to assess the comparative efficacy of treatments among patients with previously treated advanced or metastatic NSCLC.

Methods

Randomized trials of dabrafenib + trametinib, docetaxel, erlotinib, nintedanib + docetaxel, nivolumab, pemetrexed, pembrolizumab, and best supportive care as second-line or above treatments for advanced or metastatic NSCLC identified in a systematic literature review were included in the NMA. Overall response rates (ORRs) and disease control rates (DCRs) were compared using logit models; progression-free survival (PFS) and overall survival (OS) were compared using fractional polynomial hazards models. Dabrafenib + trametinib was linked into the evidence network through a matching-adjusted indirect comparison versus nivolumab.

Results

Ten trials met the inclusion criteria and were included in the NMA. Dabrafenib + trametinib, pembrolizumab, and nivolumab were associated with the highest odds of achieving overall response (12.2, 1.2, and 0.7 times higher, respectively, compared with docetaxel). Estimated DCR was higher for dabrafenib + trametinib, nintedanib + docetaxel, and pemetrexed compared with other treatments. Patients treated with dabrafenib + trametinib, nivolumab, and pembrolizumab had the lowest hazards of disease progression or death during follow-up (72, 61, and 29% lower hazard of progression at 6 months; 61, 48, and 46% lower hazard of death at 1 year, respectively, compared with docetaxel).

Conclusion

Dabrafenib + trametinib, pembrolizumab, and nivolumab were associated with higher ORR and prolonged PFS and OS compared with chemotherapy in previously treated advanced or metastatic NSCLC.

Funding

Novartis Pharmaceuticals Corporation.

Keywords

Comparative efficacy Dabrafenib Network meta-analysis Non-small-cell lung cancer Trametinib 

Notes

Acknowledgements

Funding

Sponsorship for this study and article processing charges were funded by Novartis Pharmaceuticals Corporation.

Medical Writing Assistance

Medical writing assistance was provided by Shelley Batts, PhD, an employee of Analysis Group, Inc. Support for this assistance was funded by Novartis Pharmaceuticals Corporation.

Authorship

All authors had full access to all of the data in this study and take complete responsibility for the integrity of the data and accuracy of the data analysis. All named authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship of this article, take responsibility for the integrity of the work as a whole, and have given their approval for this version to be published.

Author Contributions

JL, JZ, VGH, MLR, ZZ, and JS extracted the data from the included studies and performed the network meta-analysis. All authors analyzed and interpreted the data. The manuscript was collectively written by all authors with editorial assistance from a professional medical writer. All authors read and approved the final manuscript. All authors agree to be accountable for all aspects of the work.

Disclosures

Pingkuan Zhang is an employee of Novartis Pharmaceuticals Corp. and owns stock/stock options. Medha Sasane was an employee of Novartis at the time of the study’s conduct and is currently an employee of Sanofi-Aventis. Junlong Li is an employee of Analysis Group, Inc., which has received consultancy fees from Novartis Pharmaceuticals Corporation. Jing Zhao is an employee of Analysis Group, Inc., which has received consultancy fees from Novartis Pharmaceuticals Corp. Viviana Garcia Horton is an employee of Analysis Group, Inc., which has received consultancy fees from Novartis Pharmaceuticals Corp. Marie Louise Ricculli is an employee of Analysis Group, Inc., which has received consultancy fees from Novartis Pharmaceuticals Corp. Zheng-Yi Zhou is an employee of Analysis Group, Inc., which has received consultancy fees from Novartis Pharmaceuticals Corp. James Signorovitch is an employee of Analysis Group, Inc., which has received consultancy fees from Novartis Pharmaceuticals Corp.

Compliance with Ethics Guidelines

This study is a secondary analysis of the dabrafenib + trametinib trial data and previously published information; no institutional board review was required.

Data Availability

Data sharing is not applicable to this article because of the confidentiality agreement of the dabrafenib + trametinib trial. No data sets were generated or analyzed for other trials during the study.

Supplementary material

12325_2018_734_MOESM1_ESM.docx (269 kb)
Supplementary material 1 (DOCX 2459 kb)

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Copyright information

© Springer Healthcare Ltd., part of Springer Nature 2018

Authors and Affiliations

  • Junlong Li
    • 1
    Email author
  • Medha Sasane
    • 2
  • Jing Zhao
    • 1
  • Viviana Garcia Horton
    • 3
  • Pingkuan Zhang
    • 2
  • Marie Louise Ricculli
    • 3
  • Zheng-Yi Zhou
    • 3
  • James Signorovitch
    • 1
  1. 1.Analysis Group Inc.BostonUSA
  2. 2.Novartis Pharmaceuticals CorporationEast HanoverUSA
  3. 3.Analysis Group Inc.New YorkUSA

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