Meta-analysis of single-agent chemotherapy compared with combination chemotherapy as second-line treatment of advanced non-small-cell lung cancer
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 METHODS: We performed meta-analysis of individual patient data from randomized trials, both published and unpublished, comparing single-agent with doublet chemotherapy as second-line treatment of advanced NSCLC.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.
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Combination chemotherapy regimens have not shown an OS benefit over single-agent treatments.
“Combination chemotherapy regimens failed to show any OS benefit over single-agent treatments [85].”
From Metastatic non-small-cell lung cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up (2016) · cites this paper as [85]
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- Authors
- 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.
- Affiliations
- From the Clinical Trials Unit, National Cancer Institute; Department of Medicine and Public Health, Second University of Napoli; Division of Medical Oncology, “N.Giannettasio” Hospital, Rossano; La Maddalena, University of Palermo; Division of Medical Oncology, “S. Giuseppe Moscati” Hospital, Avellino, Italy; Department of Medical Oncology, University General Hospital, Heraklion, Crete, Greece; Osaka City General Hospital, Osaka, Japan; Department of Pulmonology, University Medical Center, Groningen; and...
- University Medical Center Groningen (NL)
- ORCID
- Venue
- Journal of Clinical Oncology
- Published
- 2009-04-10
- Volume
- 27
- Issue
- 11
- Pages
- 1836-1843
- ISSN
- 0732-183X (ISSN-L)
- 1527-7755
- OpenAlex
- W2120031407
- Cited by
- 181
- References
- 23
- Citations by year
- 2026: 3 · 2025: 2 · 2024: 5 · 2023: 5 · 2022: 2 · 2021: 6 · 2020: 4 · 2019: 10 · 2018: 8 · 2017: 13 · 2016: 14 · 2015: 24 · 2014: 18 · 2013: 16 · 2012: 17
- FWCI
- 2.53
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Clinical Oncology (publishedVersion)
- PubMed (publishedVersion)
- Amsterdam UMC (VU Amsterdam) - Institutional Repository (publishedVersion)
- Archivio Istituzionale della Ricerca - Università degli Studi della Campania "Luigi Vanvitelli" (submittedVersion)
- Institutional Research Information System University of Turin (University of Turin) (submittedVersion)
- Pure Amsterdam UMC (submittedVersion)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Treatments and Mutations
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Diagnosis and Treatment
- Health Sciences › Medicine › Oncology › Lung Cancer Research Studies
- Keywords
- non-small cell lung cancer, second-line chemotherapy, doublet chemotherapy, single-agent chemotherapy, overall survival, progression-free survival, response rate, chemotherapy toxicity, hematologic toxicity, individual patient data
- MeSH terms
- Adult, Aged, Antineoplastic Agents, Antineoplastic Combined Chemotherapy Protocols, Carcinoma, Non-Small-Cell Lung, Female, Humans, Lung Neoplasms, Male, Middle Aged, Survival Analysis, Young Adult
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