Chemotherapy in addition to supportive care improves survival in advanced non-small-cell lung cancer: a systematic review and meta-analysis of individual patient data from 16 randomized controlled trials

Abstract

Purpose: Since our individual patient data (IPD) meta-analysis (MA) of supportive care and chemotherapy for non-small-cell lung cancer (NSCLC), published in 1995, many trials have been completed. An updated, IPD MA has been carried out to assess newer regimens and determine conclusively the effect of chemotherapy.

Methods: Systematic searches for randomized controlled trials (RCTs) were undertaken, followed by central collection, checking, and reanalysis of updated IPD. Results from RCTs were combined to calculate individual and pooled hazard ratios (HRs).

Results: Data were obtained from 2,714 patients from 16 RCTs. There were 1,293 deaths among 1,399 patients assigned supportive care and chemotherapy and 1,240 among 1,315 assigned supportive care alone. Results showed a significant benefit of chemotherapy (HR, 0.77; 95% CI, 0.71 to 0.83; P <or= .0001), equivalent to a relative increase in survival of 23% or an absolute improvement in survival of 9% at 12 months, increasing survival from 20% to 29%. There was no clear evidence that this effect was influenced by the drugs used (P = .63) or whether they were used as single agents or in combination (P = .40). Despite changes in patient demographics, the effect of chemotherapy in recent trials did not differ from those included previously (P = .77). There was no clear evidence of a difference or trend in the relative effect of chemotherapy across patient subgroups.

Conclusion: This MA of chemotherapy in the supportive care setting demonstrates conclusively that chemotherapy improves overall survival in all patients with advanced NSCLC. Therefore, all patients who are fit enough and wish to receive chemotherapy should do so.

Fig 1.

Hazard ratio plot of effect of chemotherapy on survival. Each trial is represented by a blue square, the center of which denotes the hazard ratio for that trial with the horizontal lines showing the 99% and 95% CIs. The size of the square is directly proportional to amount of information in the trial. The red diamond gives the overall hazard ratio for combined results of all trials; the center denotes the hazard ratio and the extremities the 95% CI. The yellow diamonds represent hazard ratios for the trial groups; the center denotes the hazard ratio and the extremities the 95% CI. SC, supportive care; CT, chemotherapy; NCIC CTG, National Cancer Institute of Canada Clinical Trials Group; NRH, Norwegian Radium Hospital; CEP-85, Cerce d'etudes pneumologiques; UCLA, University of California—Los Angeles; JLCSG, Joint Lung Cancer Study Group; BLT, Big Lung Trial; AOI, Associazione Oncologia Italiana; MIC2, mitomycin, ifosfamide, and cisplatin; ELVIS, Elderly Lung Cancer Vinorebine Italian Study Group.

Fig 2.

Simple (nonstratified) Kaplan-Meier curve for survival by treatment. SC, supportive care; CT, chemotherapy.

Fig 3.

Effect of chemotherapy on survival by age, sex, stage, histology, and performance status.