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Is There a Survival Benefit of First-Line Epidermal Growth Factor Receptor Tyrosine-Kinase Inhibitor Monotherapy Versus Chemotherapy in Patients with Advanced Non-Small-Cell Lung Cancer?: A Meta-Analysis

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Abstract

Background

Tyrosine-kinase inhibitors (TKIs) markedly improve progression-free survival (PFS) of patients with advanced non-small-cell lung cancer (NSCLC) mutated for epidermal growth factor receptor (EGFR). Results on overall survival (OS) are less clear-cut. We performed a publication-based meta-analysis to address further this issue.

Methods

We did a PubMed query using keywords simultaneously (lung neoplasm, tyrosine kinase inhibitors, epidermal growth factor receptor mutation, survival, and randomized controlled trials). We also searched for relevant abstracts in annual proceedings of ASCO, ESMO, and WCLC meetings. We cross-checked all references from all eligible articles. Only phase III randomized controlled trials comparing TKI monotherapy and platinum-based doublet chemotherapy in first-line treatment of metastatic or advanced NSCLC were included. We used EasyMA software to perform statistical analyses. A random effect model was used in case of heterogeneity between studies (and a fixed effect model in absence of heterogeneity).

Results

The eight eligible studies included 2962 patients (780 males, 2182 females, mostly Asian, median age 60 years), 2909 adenocarcinomas (98 %), 1739 mutated tumors (897 exon 19 deletion, 699 L858 mutation), 448 stage IIIB, and 2222 stage IV (75 %) tumours and 2453 never smokers (83 %). Four studies assessed gefitinib, two studies assessed erlotinib, and two studies assessed afatinib. Chemotherapies were doublets including a platinum salt. All studies included patients with EGFR mutations, but six studies included only EGFR mutated patients. OS was similar among patients who first received TKI or chemotherapy (HR 0.98, 95 % CI 0.87-1.10, fixed effect model). Conversely, compared with chemotherapy, EGFR TKIs significantly improved PFS in patients with EGFR-mutated tumours (HR 0.37, 95 % CI 0.29-0.49, random effect model). Concerning side effects, rash (RR 6.29, 95 % CI 4.05-9.77), diarrhoea (RR 3.51, 95 % CI 2.15-5.75), stomatitis (RR 3.57, 95 % CI 1.81-7.04), and interstitial lung disease (RR 6.07, 95 % CI 1.66-22.2) were significantly more frequent after TKIs. As expected, fatigue (RR 0.38, 95 % CI 0.32-0.45), nausea/vomiting (RR 0.19, 95 % CI 0.11-0.32), and haematological disorders, including thrombocytopenia (RR 0.18, 95 % CI 0.09-0.35), anaemia (RR 0.22, 95 % CI 0.15-0.33), and grade 3-4 neutropenia (RR 0.06, 95 % CI 0.04-0.08), were significantly more frequent after chemotherapy.

Conclusion

The major discrepancy between a similar OS and a markedly improved PFS after first-line TKI compared with chemotherapy could be related to the high level of crossing-over between both groups.

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Conflict of Interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Oncology, Avicenne Hospital, HUPSSD, AP-HP, 125 route de Stalingrad, 93009, Bobigny, France

    Gaetan Des Guetz, Kader Chouahnia & Jean-François Morere

  2. Unité de Coordination en Onco-Gériatrie (UCOG), HUPSSD, AP-HP, Sevran, France

    Thierry Landre

  3. Department of Pharmacology, Avicenne Hospital, HUPSSD, AP-HP, Bobigny, France

    Bernard Uzzan & Patrick Nicolas

  4. Department of Geriatric Oncology, René Muret hospital, HUPSSD, AP-HP, Avenue du Dr Schaeffner, 93270, Sevran, France

    Thierry Landre

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  1. Gaetan Des Guetz
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Correspondence to Thierry Landre.

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Guetz, G.D., Landre, T., Uzzan, B. et al. Is There a Survival Benefit of First-Line Epidermal Growth Factor Receptor Tyrosine-Kinase Inhibitor Monotherapy Versus Chemotherapy in Patients with Advanced Non-Small-Cell Lung Cancer?: A Meta-Analysis. Targ Oncol 11, 41–47 (2016). https://doi.org/10.1007/s11523-015-0373-x

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  • DOI: https://doi.org/10.1007/s11523-015-0373-x

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