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Impact of Third-Generation Drugs on the Activity of First-Line Chemotherapy in Advanced Non-Small Cell Lung Cancer: A Meta-Analytical Approach

^aMedical Oncology A, Disease Management Team - Lung Cancer, National Institute for Cancer Research, Genova, Italy; ^bDepartment of Medical Oncology, University Hospital of Udine, Piazzale S. M. della Misericordia, Udine, Italy; ^cDepartment of Medical Oncology, Mirano Hospital, Via L. Mariutto, Mirano, VE, Italy

Key Words. Non-small-cell lung carcinoma • Meta-analysis • Gemcitabine • Docetaxel • Paclitaxel • Vinorelbine

Correspondence: Correspondence: Francesco Grossi, M.D., Medical Oncology A, Disease Management Team - Lung Cancer, National Institute for Cancer Research, Largo R. Benzi, 10, 16132 Genova, Italy. Telephone: 39-010-560-06-65 (office) or 39-335-525-54-84 (mobile); Fax: 39-010-560-08-50; e-mail: francesco.grossi{at}istge.it

Received December 1, 2008; accepted for publication March 24, 2009.

Disclosure: Employment/leadership position: None; Intellectual property rights/inventor/patent holder: None; Consultant/advisory role: None; Honoraria: Francesco Grossi, Eli Lilly, Sanofi-Aventis, Roche; Gianpiero Fasola, Roche, Eli Lilly, Sanofi-Aventis; Giovanni Pappagallo, Eli Lilly, Sanofi-Aventis; Research funding/contracted research: None; Ownership interest: None; Expert testimony: None; Other: None. The content of this article has been reviewed by independent peer reviewers to ensure that it is balanced, objective, and free from commercial bias. No financial relationships relevant to the content of this article have been disclosed by the authors, planners, independent peer reviewers, or staff managers.

Background. The therapeutic equivalence of different third-generation agents in the first-line treatment of advanced non-small cell lung cancer (NSCLC) has long been accepted, although recent studies seem to suggest some superiority of gemcitabine- or docetaxel-containing regimens over other third-generation doublets.

Objective. To assess the relative impact of different third-generation drugs on the activity of first-line chemotherapy in advanced non-small cell lung cancer by considering both response and progressive disease (PD) rates as outcome measures.

Methods. Published and unpublished data were collected from randomized trials comparing a gemcitabine-, docetaxel-, vinorelbine- or paclitaxel-containing regimen with one or more gemcitabine-, docetaxel-, vinorelbine- or paclitaxel-free combinations. For each study, 2 x 2 tables were constructed for both response and immediate progression. Pooled odds ratios were calculated using a general variance-based method.

Results. Forty-five trials (11,867 patients) were eligible. The odds of obtaining an overall response to treatment were similar across different regimens. Gemcitabine-based chemotherapy was associated with a 14% lower risk for immediate progression, whereas patients receiving paclitaxel showed a 22% higher risk for having PD as the best response. Docetaxel treatment provided a nonsignificant 9% lower odds for progression.

Conclusions. These data demonstrate that different third-generation regimens have comparable activity in chemotherapy-naïve patients with advanced NSCLC. Gemcitabine-based chemotherapy provides better disease control, whereas the risk for immediate progression is significantly higher when paclitaxel-containing regimens are used.