Chest
Volume 135, Issue 6, June 2009, Pages 1596-1609
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Original Research
Lung Cancer
Second-Line Treatments in Non-small Cell Lung Cancer: A Systematic Review of Literature and Metaanalysis of Randomized Clinical Trials

https://doi.org/10.1378/chest.08-1503Get rights and content

Background

To assess the efficacy of second-line treatments in non-small cell lung cancer.

Methods

A systematic review of literature with metaanalysis of randomized clinical trials was independently performed by three authors. A primary analysis included all RCTs comparing any approach with placebo; a secondary analysis included all RCTs comparing any treatment with docetaxel therapy every 3 weeks. The 1-year survival rate of the primary analysis was the primary outcome of the study; the 1-year SR of the secondary analysis, response rate (RR), and time to progression of primary and secondary analyses were the secondary end points.

Results

Fourteen RCTs met the selection criteria. The outcomes of 2,627 and 5,952 patients were analyzed in the primary and secondary analysis, respectively. A significant heterogeneity was documented in the primary analysis for 1-year SR with odd ratio [OR] = 0.763 (p = 0.029). No heterogeneity was documented for RR in the primary analysis, with OR = 0.165 (p < 0.001). A modest heterogeneity was documented in the secondary analysis for 1-year SR and RR, with 1-year SR OR = 0.924 (p = 0.122) and RR OR = 1.069 (p = 0.643).

Conclusion

Second-line treatments in NSCLC seem to improve the main outcomes better than supportive care. Docetaxel administration every 3 weeks probably remains the “gold standard” because at present the data in literature are not enough to support a greater efficacy of other alternative options. Further trials are needed to identify a clinical and biological profile that could predict the response to treatments and a criterion to select the patients to be treated with chemotherapy or EGFR inhibitors.

Section snippets

Search Criteria and Systematic Review of Literature

A systematic review of MEDLINE, EMBASE, CINAHL, CRISP, and Cochrane Systematic Reviews databases from January 2000 to July 2008 was independently performed by two authors (D.T. and L.L.A.), using “Carcinoma, Non Small-Cell Lung” (medical subject heading [MeSH] term) and “Drug Therapy” (MeSH term) and “docetaxel” (MeSH term) or “erlotinib” (MeSH term) or “gefitinib” (MeSH term) as search terms. A primary analysis was planned to compare the outcomes of antineoplastic treatments vs BSC, and a

Literature Review

We retrieved and examined 336 descriptive reviews, 104 clinical trials, and 8 systematic reviews with metaanalysis in the preliminary evaluation. Fifteen of these 448 articles (all of them reporting data of randomized phase III clinical trials) were considered potentially eligible because they reported mature data comparing different therapeutic options in second-line treatment of NSCLC, and 14 were included into the analysis. Two of the 15 potentially eligible studies3, 19 reported data from

Discussion

In the last few years, many authors have investigated the role of second-line therapies in advanced NSCLC,14, 15, 25, 26, 27 and different options were recommended by the primary scientific societies as the “gold standard.”1, 2, 4, 5 Based on these recommendations, docetaxel or pemetrexed represent the main chemotherapeutic options, and erlotinib is the biological alternative to chemotherapy, mainly in no-smoker females with adenocarcinoma.14, 15, 25, 26, 27 However, some issues remain

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    The authors have reported to the ACCP that no significant conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article.

    Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (www.chestjournal.org/site/misc/reprints.xhtml).

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