Meta-Analysis of Single-Agent Chemotherapy Compared With Combination Chemotherapy As Second-Line Treatment of Advanced Non-Small-Cell Lung Cancer

Massimo Di Maio; Paolo Chiodini; Vassilis Georgoulias; Dora Hatzidaki; Koji Takeda; Floris M. Wachters; Vittorio Gebbia; Egbert F. Smit; Alessandro Morabito; Ciro Gallo; Francesco Perrone; Cesare Gridelli

doi:10.1200/JCO.2008.17.5844

Meta-Analysis of Single-Agent Chemotherapy Compared With Combination Chemotherapy As Second-Line Treatment of Advanced Non-Small-Cell Lung Cancer

Massimo Di Maio, Paolo Chiodini, Vassilis Georgoulias, Dora Hatzidaki, Koji Takeda, Floris M. Wachters, Vittorio Gebbia, Egbert F. Smit, Alessandro Morabito, Ciro Gallo, Francesco Perrone, Cesare Gridelli^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

164 Citations (Scopus)

Abstract

Purpose

Doublet chemotherapy is more effective than single-agent as first-line treatment of advanced non-small-cell lung cancer (NSCLC). As second-line treatment, several randomized trials have been performed comparing single-agent with doublet chemotherapy, but each trial had an insufficient power to detect potentially relevant differences in survival.

Methods

We performed meta-analysis of individual patient data from randomized trials, both published and unpublished, comparing single-agent with doublet chemotherapy as second-line treatment of advanced NSCLC. Primary end point was overall survival (OS). All statistical analyses were stratified by trial.

Results

Eight eligible trials were identified. Data of two trials were not available, and data of six trials (847 patients) were collected. Median age was 61 years. Performance status was 0 or 1 in 90%; 80% of patients had received previous platin-based chemotherapy. OS was not significantly different between arms (P = .32). Median OS was 37.3 and 34.7 weeks in the doublet and single-agent arms, respectively. Hazard ratio (HR) was 0.92 (95% CI, 0.79 to 1.08). Response rate was 15.1% with doublet and 7.3% with single-agent (P = .0004). Median progression-free survival was 14 weeks for doublet and 11.7 weeks for single agent (P = .0009; HR, 0.79; 95% CI, 0.68 to 0.91). There was no significant heterogeneity among trials for the three efficacy outcomes. Patients treated with doublet chemotherapy had significantly more grade 3 to 4 hematologic (41% v 25%; P = .0001) and grade 3 to 4 nonhematologic toxicity (28% v 22%; P = .034).

Conclusion

Doublet chemotherapy as second-line treatment of advanced NSCLC significantly increases response rate and progression-free survival, but is more toxic and does not improve overall survival compared to single-agent. J Clin Oncol 27: 1836-1843. (C) 2009 by American Society of Clinical Oncology

Original language	English
Pages (from-to)	1836-1843
Number of pages	8
Journal	Journal of Clinical Oncology
Volume	27
Issue number	11
DOIs	https://doi.org/10.1200/JCO.2008.17.5844
Publication status	Published - 10-Apr-2009

Keywords

RANDOMIZED PHASE-II
PATIENT DATA METAANALYSIS
DOCETAXEL
TRIAL
IRINOTECAN
MULTICENTER
GEMCITABINE
CISPLATIN
TIME

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Di Maio, M., Chiodini, P., Georgoulias, V., Hatzidaki, D., Takeda, K., Wachters, F. M., Gebbia, V., Smit, E. F., Morabito, A., Gallo, C., Perrone, F., & Gridelli, C. (2009). Meta-Analysis of Single-Agent Chemotherapy Compared With Combination Chemotherapy As Second-Line Treatment of Advanced Non-Small-Cell Lung Cancer. Journal of Clinical Oncology, 27(11), 1836-1843. https://doi.org/10.1200/JCO.2008.17.5844

@article{9caeb20dd20e4a7b8e1e4d02403a5960,

title = "Meta-Analysis of Single-Agent Chemotherapy Compared With Combination Chemotherapy As Second-Line Treatment of Advanced Non-Small-Cell Lung Cancer",

abstract = "PurposeDoublet chemotherapy is more effective than single-agent as first-line treatment of advanced non-small-cell lung cancer (NSCLC). As second-line treatment, several randomized trials have been performed comparing single-agent with doublet chemotherapy, but each trial had an insufficient power to detect potentially relevant differences in survival.MethodsWe performed meta-analysis of individual patient data from randomized trials, both published and unpublished, comparing single-agent with doublet chemotherapy as second-line treatment of advanced NSCLC. Primary end point was overall survival (OS). All statistical analyses were stratified by trial.ResultsEight eligible trials were identified. Data of two trials were not available, and data of six trials (847 patients) were collected. Median age was 61 years. Performance status was 0 or 1 in 90%; 80% of patients had received previous platin-based chemotherapy. OS was not significantly different between arms (P = .32). Median OS was 37.3 and 34.7 weeks in the doublet and single-agent arms, respectively. Hazard ratio (HR) was 0.92 (95% CI, 0.79 to 1.08). Response rate was 15.1% with doublet and 7.3% with single-agent (P = .0004). Median progression-free survival was 14 weeks for doublet and 11.7 weeks for single agent (P = .0009; HR, 0.79; 95% CI, 0.68 to 0.91). There was no significant heterogeneity among trials for the three efficacy outcomes. Patients treated with doublet chemotherapy had significantly more grade 3 to 4 hematologic (41% v 25%; P = .0001) and grade 3 to 4 nonhematologic toxicity (28% v 22%; P = .034).ConclusionDoublet chemotherapy as second-line treatment of advanced NSCLC significantly increases response rate and progression-free survival, but is more toxic and does not improve overall survival compared to single-agent. J Clin Oncol 27: 1836-1843. (C) 2009 by American Society of Clinical Oncology",

keywords = "RANDOMIZED PHASE-II, PATIENT DATA METAANALYSIS, DOCETAXEL, TRIAL, IRINOTECAN, MULTICENTER, GEMCITABINE, CISPLATIN, TIME",

author = "{Di Maio}, Massimo and Paolo Chiodini and Vassilis Georgoulias and Dora Hatzidaki and Koji Takeda and Wachters, {Floris M.} and Vittorio Gebbia and Smit, {Egbert F.} and Alessandro Morabito and Ciro Gallo and Francesco Perrone and Cesare Gridelli",

year = "2009",

month = apr,

day = "10",

doi = "10.1200/JCO.2008.17.5844",

language = "English",

volume = "27",

pages = "1836--1843",

journal = "Journal of Clinical Oncology",

issn = "0732-183X",

publisher = "AMER SOC CLINICAL ONCOLOGY",

number = "11",

}

Di Maio, M, Chiodini, P, Georgoulias, V, Hatzidaki, D, Takeda, K, Wachters, FM, Gebbia, V, Smit, EF, Morabito, A, Gallo, C, Perrone, F & Gridelli, C 2009, 'Meta-Analysis of Single-Agent Chemotherapy Compared With Combination Chemotherapy As Second-Line Treatment of Advanced Non-Small-Cell Lung Cancer', Journal of Clinical Oncology, vol. 27, no. 11, pp. 1836-1843. https://doi.org/10.1200/JCO.2008.17.5844

Meta-Analysis of Single-Agent Chemotherapy Compared With Combination Chemotherapy As Second-Line Treatment of Advanced Non-Small-Cell Lung Cancer. / Di Maio, Massimo; Chiodini, Paolo; Georgoulias, Vassilis et al.
In: Journal of Clinical Oncology, Vol. 27, No. 11, 10.04.2009, p. 1836-1843.

Research output: Contribution to journal › Article › Academic › peer-review

TY - JOUR

T1 - Meta-Analysis of Single-Agent Chemotherapy Compared With Combination Chemotherapy As Second-Line Treatment of Advanced Non-Small-Cell Lung Cancer

AU - Di Maio, Massimo

AU - Chiodini, Paolo

AU - Georgoulias, Vassilis

AU - Hatzidaki, Dora

AU - Takeda, Koji

AU - Wachters, Floris M.

AU - Gebbia, Vittorio

AU - Smit, Egbert F.

AU - Morabito, Alessandro

AU - Gallo, Ciro

AU - Perrone, Francesco

AU - Gridelli, Cesare

PY - 2009/4/10

Y1 - 2009/4/10

N2 - PurposeDoublet chemotherapy is more effective than single-agent as first-line treatment of advanced non-small-cell lung cancer (NSCLC). As second-line treatment, several randomized trials have been performed comparing single-agent with doublet chemotherapy, but each trial had an insufficient power to detect potentially relevant differences in survival.MethodsWe performed meta-analysis of individual patient data from randomized trials, both published and unpublished, comparing single-agent with doublet chemotherapy as second-line treatment of advanced NSCLC. Primary end point was overall survival (OS). All statistical analyses were stratified by trial.ResultsEight eligible trials were identified. Data of two trials were not available, and data of six trials (847 patients) were collected. Median age was 61 years. Performance status was 0 or 1 in 90%; 80% of patients had received previous platin-based chemotherapy. OS was not significantly different between arms (P = .32). Median OS was 37.3 and 34.7 weeks in the doublet and single-agent arms, respectively. Hazard ratio (HR) was 0.92 (95% CI, 0.79 to 1.08). Response rate was 15.1% with doublet and 7.3% with single-agent (P = .0004). Median progression-free survival was 14 weeks for doublet and 11.7 weeks for single agent (P = .0009; HR, 0.79; 95% CI, 0.68 to 0.91). There was no significant heterogeneity among trials for the three efficacy outcomes. Patients treated with doublet chemotherapy had significantly more grade 3 to 4 hematologic (41% v 25%; P = .0001) and grade 3 to 4 nonhematologic toxicity (28% v 22%; P = .034).ConclusionDoublet chemotherapy as second-line treatment of advanced NSCLC significantly increases response rate and progression-free survival, but is more toxic and does not improve overall survival compared to single-agent. J Clin Oncol 27: 1836-1843. (C) 2009 by American Society of Clinical Oncology

AB - PurposeDoublet chemotherapy is more effective than single-agent as first-line treatment of advanced non-small-cell lung cancer (NSCLC). As second-line treatment, several randomized trials have been performed comparing single-agent with doublet chemotherapy, but each trial had an insufficient power to detect potentially relevant differences in survival.MethodsWe performed meta-analysis of individual patient data from randomized trials, both published and unpublished, comparing single-agent with doublet chemotherapy as second-line treatment of advanced NSCLC. Primary end point was overall survival (OS). All statistical analyses were stratified by trial.ResultsEight eligible trials were identified. Data of two trials were not available, and data of six trials (847 patients) were collected. Median age was 61 years. Performance status was 0 or 1 in 90%; 80% of patients had received previous platin-based chemotherapy. OS was not significantly different between arms (P = .32). Median OS was 37.3 and 34.7 weeks in the doublet and single-agent arms, respectively. Hazard ratio (HR) was 0.92 (95% CI, 0.79 to 1.08). Response rate was 15.1% with doublet and 7.3% with single-agent (P = .0004). Median progression-free survival was 14 weeks for doublet and 11.7 weeks for single agent (P = .0009; HR, 0.79; 95% CI, 0.68 to 0.91). There was no significant heterogeneity among trials for the three efficacy outcomes. Patients treated with doublet chemotherapy had significantly more grade 3 to 4 hematologic (41% v 25%; P = .0001) and grade 3 to 4 nonhematologic toxicity (28% v 22%; P = .034).ConclusionDoublet chemotherapy as second-line treatment of advanced NSCLC significantly increases response rate and progression-free survival, but is more toxic and does not improve overall survival compared to single-agent. J Clin Oncol 27: 1836-1843. (C) 2009 by American Society of Clinical Oncology

KW - RANDOMIZED PHASE-II

KW - PATIENT DATA METAANALYSIS

KW - DOCETAXEL

KW - TRIAL

KW - IRINOTECAN

KW - MULTICENTER

KW - GEMCITABINE

KW - CISPLATIN

KW - TIME

U2 - 10.1200/JCO.2008.17.5844

DO - 10.1200/JCO.2008.17.5844

M3 - Article

SN - 0732-183X

VL - 27

SP - 1836

EP - 1843

JO - Journal of Clinical Oncology

JF - Journal of Clinical Oncology

IS - 11

ER -

Meta-Analysis of Single-Agent Chemotherapy Compared With Combination Chemotherapy As Second-Line Treatment of Advanced Non-Small-Cell Lung Cancer

Abstract

Keywords

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