Maintenance or consolidation therapy in small-cell lung cancer: A systematic review and meta-analysis

Rossi, Antonio; Garassino, Marina Chiara; Cinquini, Michela; Sburlati, Paola; Di Maio, Massimo; Farina, Gabriella; Gridelli, Cesare; Torri, Valter

doi:10.1016/j.lungcan.2010.02.001

« Previous Next »Lung Cancer
Volume 70, Issue 2 , Pages 119-128, November 2010

Maintenance or consolidation therapy in small-cell lung cancer: A systematic review and meta-analysis

Antonio Rossi
- Division of Medical Oncology, “S.G. Moscati” Hospital, Città Ospedaliera, Contrada Amoretta 8, 83100 Avellino, Italy
- Corresponding author. Tel.: +39 0825 203573; fax: +39 0825 203556.
Marina Chiara Garassino
- Oncology Department, “Fatebenefratelli and Oftalmico” Hospital, Milan, Italy
Michela Cinquini
- Laboratory of New Drug Development Strategies, Oncology Department, “Mario Negri” Institute, Milan, Italy
Paola Sburlati
- Oncology Department, “Fatebenefratelli and Oftalmico” Hospital, Milan, Italy
Massimo Di Maio
- Clinical Trials Unit, National Cancer Institute, “G. Pascale” Foundation, Naples, Italy
Gabriella Farina
- Oncology Department, “Fatebenefratelli and Oftalmico” Hospital, Milan, Italy
Cesare Gridelli
- Division of Medical Oncology, “S.G. Moscati” Hospital, Città Ospedaliera, Contrada Amoretta 8, 83100 Avellino, Italy
Valter Torri
- Laboratory of New Drug Development Strategies, Oncology Department, “Mario Negri” Institute, Milan, Italy

Received 9 May 2009; received in revised form 9 September 2009; accepted 1 February 2010. published online 26 February 2010.

Abstract

Objective

To assess the role of maintenance or consolidation therapy in the treatment of small-cell lung cancer (SCLC), a meta-analysis of all published randomized clinical trials (RCTs) was performed in order to provide an overall meta-analysis and indirectly compare the effect of chemotherapy, interferons, and other biologic agents.

Methods

Electronic databases were searched for publication reporting of RCTs comparing maintenance or consolidation therapy versus placebo or follow-up alone until December 2008. Hazard ratios (HRs) for progression-free survival (PFS) and overall survival (OS), with their relative 95% confidence intervals (CI), were derived. In the calculation of HRs, the “no maintenance” arm served as a reference. The a priori value of p<0.05 was chosen as significant level for statistical tests.

Results

Twenty-one RCTs, encompassing 3,688 patients, were eligible for the present analysis: 11 RCTs employing chemotherapy, 6 interferons (4 alpha and 2 gamma), and 4 other biological agents. Overall, no statistical advantage in OS (HR 0.93, 95% CI 0.87–1.00; p=0.05) or in PFS (HR 0.98, 95% CI 0.91–1.06; p=0.63) was reported for maintenance or consolidation therapy. Statistical evidence of different effects among the four types of therapy was detected for OS (χ² test for heterogeneity: 8.07 [3 df]; p=0.04), but not for PFS. A statistically significant reduction of mortality was detected in those studies assessing the efficacy of chemotherapy (HR 0.89, 95% CI 0.81–0.98; p=0.02) and of interferon-alpha (HR 0.78, 95% CI 0.64–0.96; p=0.02).

Conclusions

The maintenance or the consolidation approach failed to improve the outcomes of SCLC. A survival advantage is suggested for maintenance chemotherapy and interferon-alpha, but its clinical impact needs to be confirmed by further studies.

Keywords: SCLC, Maintenance therapy, Consolidation therapy, Meta-analysis, Targeted therapy, Immunotherapy, Chemotherapy