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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

Davide Tassinari, MD; Emanuela Scarpi, PhD; Sergio Sartori, MD; Emiliano Tamburini, MD; Carlotta Santelmo, MD; Paola Tombesi, MD; Luigi Lazzari-Agli, MD
Author and Funding Information

*From the Department of Oncology (Drs. Tassinari, Tamburini, and Santelmo), City Hospital, Rimini, Italy; Institute of Research and Study of Tumours of Romagna (Dr. Scarpi), Meldola, Italy; the Department of Internal Medicine (Drs. Sartori and Tombesi), Arcispedale S. Anna, Ferrara, Italy; and the Department of Pneumology (Dr. Lazzari-Agli), City Hospital, Riccione, Italy.

Correspondence to: Davide Tassinari, MD, City Hospital, Department of Oncology, Via Settembrini 2, Rimini 47900, Italy; e-mail: dtassinari@rimini.com


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).


© 2009 American College of Chest Physicians


Chest. 2009;135(6):1596-1609. doi:10.1378/chest.08-1503
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Background:  To assess the efficacy of second-line treatments in non-small cell lung cancer (NSCLC).

Methods:  A systematic review of literature with metaanalysis of randomized clinical trials (RCTs) was independently performed by three authors. A primary analysis included all RCTs comparing any approach (chemotherapy or therapy with epidermal growth factor receptor [EGFR] inhibitors) with placebo; a secondary analysis included all RCTs comparing any treatment with docetaxel therapy every 3 weeks. The 1-year survival rate (SR) 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.

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