Phase III study of carboplatin and paclitaxel alone or with sorafenib in advanced non-small-cell lung cancer.
PURPOSE This phase III, multicenter, randomized, placebo-controlled trial assessed the efficacy and safety of sorafenib, an oral multikinase inhibitor, in combination with carboplatin and paclitaxel in chemotherapy-naïve patients with unresectable stage IIIB or IV non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS Nine hundred twenty-six patients were randomly assigned to receive up to six 21-day cycles of carboplatin area under the curve 6 and paclitaxel 200 mg/m(2) (CP) on day 1, followed by either sorafenib 400 mg twice a day (n = 464, arm A) or placebo (n = 462, arm B) on days 2 to 19. The maintenance phase after CP consisted of sorafenib 400 mg or placebo twice a day. The primary end point was overall survival (OS); secondary end points included progression-free survival and tumor response. RESULTS Overall demographics were balanced between arms; 223 patients (24%) had squamous cell histology. On the basis of a planned interim analysis, median OS was 10.7 months in arm A and 10.6 months in arm B (hazard ratio [HR] = 1.15; 95% CI, 0.94 to 1.41; P = .915). The study was terminated after the interim analysis concluded that the study was highly unlikely to meet its primary end point. A prespecified exploratory analysis revealed that patients with squamous cell histology had greater mortality in arm A than in arm B (HR = 1.85; 95% CI, 1.22 to 2.81). Main grade 3 or 4 sorafenib-related toxicities included rash (8.4%), hand-foot skin reaction (7.8%), and diarrhea (3.5%). CONCLUSION No clinical benefit was observed from adding sorafenib to CP chemotherapy as first-line treatment for NSCLC.
Scagliotti
Giorgio
G
Department of Clinical and Biological Sciences, University of Turin, San Luigi Hospital, Regione Gonzole 10, Orbassano, Torino, Italy 10043. scagliotti@ihnet.it
Novello
Silvia
S
von Pawel
Joachim
J
Reck
Martin
M
Pereira
José Rodrigues
JR
Thomas
Michael
M
Abrão Miziara
José Elias
JE
Balint
Beatrix
B
De Marinis
Filippo
F
Keller
Alan
A
Arén
Osvaldo
O
Csollak
Maria
M
Albert
Istvan
I
Barrios
Carlos Henrique
CH
Grossi
Francesco
F
Krzakowski
Maciej
M
Cupit
Lisa
L
Cihon
Frank
F
Dimatteo
Sandra
S
Hanna
Nasser
N
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000556:secondary; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001557:Benzenesulfonates / Q000008:administration & dosage; D016190:Carboplatin / Q000008:administration & dosage; D018287:Carcinoma, Large Cell / Q000188:drug therapy* / Q000556:secondary; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000556:secondary; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000556:secondary; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D009536:Niacinamide / Q000031:analogs & derivatives; D017239:Paclitaxel / Q000008:administration & dosage; D010671:Phenylurea Compounds; D010919:Placebos; D011725:Pyridines / Q000008:administration & dosage; D000077157:Sorafenib; D015996:Survival Rate; D016896:Treatment Outcome
D001557:Benzenesulfonates; D010671:Phenylurea Compounds; D010919:Placebos; D011725:Pyridines; D009536:Niacinamide; D000077157:Sorafenib; D016190:Carboplatin; D017239:Paclitaxel