Meta-analysis of concomitant versus sequential radiochemotherapy in locally advanced non-small-cell lung cancer.
OBJECTIVE
The previous individual patient data meta-analyses of chemotherapy in locally advanced non-small-cell lung cancer (NSCLC) showed that adding sequential or concomitant chemotherapy to radiotherapy improved survival. The NSCLC Collaborative Group performed a meta-analysis of randomized trials directly comparing concomitant versus sequential radiochemotherapy.


METHODS
Systematic searches for trials were undertaken, followed by central collection, checking, and reanalysis of updated individual patient data. Results from trials were combined using the stratified log-rank test to calculate pooled hazard ratios (HRs). The primary outcome was overall survival; secondary outcomes were progression-free survival, cumulative incidences of locoregional and distant progression, and acute toxicity.


RESULTS
Of seven eligible trials, data from six trials were received (1,205 patients, 92% of all randomly assigned patients). Median follow-up was 6 years. There was a significant benefit of concomitant radiochemotherapy on overall survival (HR, 0.84; 95% CI, 0.74 to 0.95; P = .004), with an absolute benefit of 5.7% (from 18.1% to 23.8%) at 3 years and 4.5% at 5 years. For progression-free survival, the HR was 0.90 (95% CI, 0.79 to 1.01; P = .07). Concomitant treatment decreased locoregional progression (HR, 0.77; 95% CI, 0.62 to 0.95; P = .01); its effect was not different from that of sequential treatment on distant progression (HR, 1.04; 95% CI, 0.86 to 1.25; P = .69). Concomitant radiochemotherapy increased acute esophageal toxicity (grade 3-4) from 4% to 18% with a relative risk of 4.9 (95% CI, 3.1 to 7.8; P < .001). There was no significant difference regarding acute pulmonary toxicity.


CONCLUSIONS
Concomitant radiochemotherapy, as compared with sequential radiochemotherapy, improved survival of patients with locally advanced NSCLC, primarily because of a better locoregional control, but at the cost of manageable increased acute esophageal toxicity.
Aupérin
Anne
A
Unit of Biostatistics and Epidemiology, Institut Gustave-Roussy, 94805 Villejuif Cedex, France. auperin@igr.fr
Le Péchoux
Cecile
C
Rolland
Estelle
E
Curran
Walter J
WJ
Furuse
Kiyoyuki
K
Fournel
Pierre
P
Belderbos
Jose
J
Clamon
Gerald
G
Ulutin
Hakki Cuneyt
HC
Paulus
Rebecca
R
Yamanaka
Takeharu
T
Bozonnat
Marie-Cecile
MC
Uitterhoeve
Apollonia
A
Wang
Xiaofei
X
Stewart
Lesley
L
Arriagada
Rodrigo
R
Burdett
Sarah
S
Pignon
Jean-Pierre
JP
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy*; D017024:Chemotherapy, Adjuvant; D016009:Chi-Square Distribution; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D004947:Esophagus / Q000187:drug effects / Q000528:radiation effects; D019317:Evidence-Based Medicine; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011829:Radiation Dosage; D018714:Radiotherapy, Adjuvant / Q000009:adverse effects; D016032:Randomized Controlled Trials as Topic; D013997:Time Factors; D016896:Treatment Outcome
D000970:Antineoplastic Agents