Purpose: To assess the comparative effectiveness and tolerability of all second-line treatments for advanced non-small cell lung cancer (NSCLC) with wild-type or unknown status for epidermal growth factor receptor (EGFR) mutations.

Primary Contributors: Perrine Créquit, Anna Chaimani, Amélie Yavchitz, Nassima Attiche, Jacques Cadranel, Ludovic Trinquart and Philippe Ravaud

Registered Protocol: PROSPERO (CRD42015017592)

Original Publication: BMC medicine. 2017 Dec;15(1):193.

 
  • Populations: Second-line treatment for EGFR wild-type (or unknown) advanced NSCLS

  • Interventions: Any

  • Comparators: Any

  • Outcomes: Overall survival, progression-free survival, objective response, safety

  • Studies: Randomized controlled trials


Main Results

  • This review currently includes 102 RCTs involving 36,058 advanced NSCLC patients with wild-type or unknown EGFR status.

  • There is differential reporting of outcomes between efficacy and safety outcomes:

    • Half of the trials report safety outcomes and less than 20% report quality of life.

  • In terms of overall survival:

    • Nivolumab is more effective than docetaxel, pemetrexed, erlotinib, and gefitinib.

    • Pembrolizumab, atezolizumab, and pemetrexed plus erlotinib are also significantly more effective than docetaxel, pemetrexed, erlotinib, and gefitinib.

  • In terms of progression-free survival:

    • Erlotinib plus cabozantinib is more effective than docetaxel, pemetrexed, erlotinib, and gefitinib.

    • Cabozantinib and pemetrexed plus erlotinib is also significantly more effective than docetaxel, pemetrexed, erlotinib, and gefitinib.

  • In terms of objective response, no treatment was significantly more effective.

  • For safety, the evidence is insufficient to draw certain conclusions.

 
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Data Sources

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Risk of Bias

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Tables

 
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Analyses

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Evidence Maps

 

Funding

This study was supported by a grant from the French National Cancer Institute (Institut National du Cancer, INCa) (N° 2016-020/058/AB-KA), and a LEGS POIX 2015 grant (from Chancellerie des Universités de Paris). The funding sources had no role in the design of this study, its execution, analyses, interpretation of the data, and decision to submit results.

Competing interests

Dr. Cadranel reports grants and personal fees from Pfizer, Novartis, and Boerhinger, and personal fees from AZ, Lilly, BMS, and Roche outside the submitted work. All other authors have no potential competing interests to disclose.


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