First-line erlotinib followed by second-line cisplatin-gemcitabine chemotherapy in advanced non-small-cell lung cancer: the TORCH randomized trial.
OBJECTIVE
Erlotinib prolonged survival of unselected patients with advanced non-small-cell lung cancer (NSCLC) who were not eligible for further chemotherapy, and two phase II studies suggested it might be an alternative to first-line chemotherapy. A randomized phase III trial was designed to test whether first-line erlotinib followed at progression by cisplatin-gemcitabine was not inferior in terms of survival to the standard inverse sequence.


METHODS
Patients with stage IIIB (with pleural effusion or supraclavicular nodes) to IV NSCLC and performance status of 0 to 1 were eligible. With a 95% CI upper limit of 1.25 for the hazard ratio (HR) for death, 80% power, a one-sided α = .025, and two interim analyses, a sample size of 900 patients was planned.


RESULTS
At the first planned interim analysis with half the events, the inferiority boundary was crossed, and the Independent Data Monitoring Committee recommended early termination of the study. Seven hundred sixty patients (median age, 62 years; range, 27 to 81 years) had been randomly assigned. Baseline characteristics were balanced between study arms. As of June 1, 2011, median follow-up was 24.3 months, and 536 deaths were recorded (263 in the standard treatment arm and 273 in the experimental arm). Median survival was 11.6 months (95% CI, 10.2 to 13.3 months) in the standard arm and 8.7 months (95% CI, 7.4 to 10.5 months) in the experimental arm. Adjusted HR of death in the experimental arm was 1.24 (95% CI, 1.04 to 1.47). There was no heterogeneity across sex, smoking habit, histotype, and epidermal growth factor receptor (EGFR) mutation.


CONCLUSIONS
In unselected patients with advanced NSCLC, first-line erlotinib followed at progression by cisplatin-gemcitabine was significantly inferior in terms of overall survival compared with the standard sequence of first-line chemotherapy followed by erlotinib.
S.G. Moscati Hospital, Avellino, Italy. cgridelli@libero.it
Cesare
C
Gridelli
Fortunato
F
Ciardiello
Ciro
C
Gallo
Ronald
R
Feld
Charles
C
Butts
Vittorio
V
Gebbia
Paolo
P
Maione
Floriana
F
Morgillo
Giovenzio
G
Genestreti
Adolfo
A
Favaretto
Natasha
N
Leighl
Rafal
R
Wierzbicki
Saverio
S
Cinieri
Yasmin
Y
Alam
Salvatore
S
Siena
Giampaolo
G
Tortora
Raffaella
R
Felletti
Ferdinando
F
Riccardi
Gianfranco
G
Mancuso
Antonio
A
Rossi
Flavia
F
Cantile
Ming-Sound
MS
Tsao
Mauro
M
Saieg
Gilda
G
da Cunha Santos
Maria Carmela
MC
Piccirillo
Massimo
M
Di Maio
Alessandro
A
Morabito
Francesco
F
Perrone
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality / Q000473:pathology; D002945:Cisplatin / Q000008:administration & dosage; D003841:Deoxycytidine / Q000031:analogs & derivatives; D018450:Disease Progression; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D066246:ErbB Receptors / Q000235:genetics; D000069347:Erlotinib Hydrochloride; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011799:Quinazolines; D000093542:Gemcitabine
D011799:Quinazolines; D003841:Deoxycytidine; D000069347:Erlotinib Hydrochloride; D066246:ErbB Receptors; D002945:Cisplatin; D000093542:Gemcitabine