Format

Send to

Choose Destination
BMC Med. 2017 Oct 30;15(1):193. doi: 10.1186/s12916-017-0954-x.

Comparative efficacy and safety of second-line treatments for advanced non-small cell lung cancer with wild-type or unknown status for epidermal growth factor receptor: a systematic review and network meta-analysis.

Créquit P1,2,3,4,5,6, Chaimani A7,8,9, Yavchitz A7,8,9,10, Attiche N7, Cadranel J11,12, Trinquart L9,13, Ravaud P7,8,14,9,15.

Author information

1
Centre de Recherche Epidémiologie et Statistique Paris Sorbonne Cité, INSERM U1153, Paris, France. perrine.crequit@aphp.fr.
2
Université Paris Descartes - Sorbonne Paris cité, Paris, France. perrine.crequit@aphp.fr.
3
Centre d'Epidémiologie Clinique, Assistance Publique-Hôpitaux de Paris, Hôpital Hôtel-Dieu, Paris, France. perrine.crequit@aphp.fr.
4
Service de Pneumologie, Assistance Publique-Hôpitaux de Paris, Hôpital Tenon, Paris, France. perrine.crequit@aphp.fr.
5
Cochrane France, Paris, France. perrine.crequit@aphp.fr.
6
Centre d'Epidémiologie Clinique, Hôpital Hôtel-Dieu, 1 place du Parvis Notre Dame, 75004, Paris, France. perrine.crequit@aphp.fr.
7
Centre de Recherche Epidémiologie et Statistique Paris Sorbonne Cité, INSERM U1153, Paris, France.
8
Université Paris Descartes - Sorbonne Paris cité, Paris, France.
9
Cochrane France, Paris, France.
10
Service d'Anesthésie-Réanimation, Hôpital Européen Georges Pompidou, Assistance Publique-Hôpitaux de Paris, Paris, France.
11
Service de Pneumologie, Assistance Publique-Hôpitaux de Paris, Hôpital Tenon, Paris, France.
12
Sorbonne Universités, UPMC Univ., Paris 06, GRC-04, Théranoscan, Paris, France.
13
Boston University School of Public Health, Department of Biostatistics, Boston, MA, USA.
14
Centre d'Epidémiologie Clinique, Assistance Publique-Hôpitaux de Paris, Hôpital Hôtel-Dieu, Paris, France.
15
Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY, USA.

Abstract

BACKGROUND:

Docetaxel, pemetrexed, erlotinib, and gefitinib are recommended as second-line treatment for advanced non-small cell lung cancer (NSCLC) with wild-type or unknown status for epidermal growth factor receptor (EGFR). However, the number of published randomized clinical trials (RCTs) on this topic is increasing. Our objective was to assess the comparative effectiveness and tolerability of all second-line treatments for advanced NSCLC with wild-type or unknown status for EGFR by a systematic review and network meta-analysis.

METHODS:

MEDLINE, EMBASE, CENTRAL, ClinicalTrials.gov, and the US Food and Drug Administration website, as well as other sources, were searched for available reports up to June 6, 2017. Two reviewers independently selected published and unpublished reports of RCTs comparing any second-line treatments, extracted data and assessed the risk of bias of all included trials. We performed a Bayesian network meta-analysis. The primary outcomes were overall survival (OS) and progression-free survival (PFS). Secondary outcomes included objective response (ObR), the number of serious adverse events, and quality of life.

RESULTS:

We included 102 RCTs involving 36,058 patients (62% male, median age 61 years, 81% with stage IV cancer, 80% smokers, and 92% with performance status 0-1). We revealed a differential reporting of outcomes between efficacy and safety outcomes. Half of the trials reported safety outcomes and less than 20% quality of life. For OS, nivolumab was more effective than docetaxel (hazard ratio (HR) 0.69, 95% credible interval (CrI) 0.56-0.83), pemetrexed (0.67, 0.52-0.83), erlotinib (0.68, 0.53-0.86), and gefitinib (0.66, 0.53-0.83). Pembrolizumab, atezolizumab, and pemetrexed plus erlotinib were also significantly more effective than docetaxel, pemetrexed, erlotinib, and gefitinib. For PFS, erlotinib plus cabozantinib was more effective than docetaxel (HR 0.39, 95% CrI 0.18-0.84), pemetrexed (0.38, 0.18-0.82), erlotinib (0.37, 0.18-0.78), and gefitinib (0.38, 0.18-0.82). Cabozantinib and pemetrexed plus erlotinib were also significantly more effective than the four recommended treatments. For ObR, no treatment was significantly more effective. The effectiveness of the four recommended treatments was similar and they were ranked among the 25 less-effective treatments. For safety, evidence is insufficient to draw certain conclusions.

CONCLUSIONS:

Nivolumab, pembrolizumab, atezolizumab, and pemetrexed plus erlotinib may be the most effective second-line treatments for NSCLC in terms of OS. The four recommended treatments seem to have relatively poor performance. However, the impact on life expectancy of immunotherapy versus other treatments should be further explored by future analyses, and more trials comparing the novel treatments are needed to reduce uncertainty in these results.

TRIAL REGISTRATION:

Registration number: PROSPERO ( CRD42015017592 ).

KEYWORDS:

Comparative effectiveness review; Immunotherapy; NSCLC; Systematic review; Treatments; Wild-type EGFR

PMID:
29082855
PMCID:
PMC5662096
DOI:
10.1186/s12916-017-0954-x
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for BioMed Central Icon for PubMed Central
Loading ...
Support Center