Pazopanib or placebo in completely resected stage I NSCLC patients: results of the phase II IFCT-0703 trial.
BACKGROUND
Adjuvant treatment in resected stage I non-small-cell lung cancer (NSCLC) is generally not recommended. Pazopanib is an oral tyrosine kinase inhibitor of VEGFR-1/2/3 and PDGFR-α/β. We explored the feasibility and efficacy of adjuvant pazopanib in this population.


METHODS
In this double-blind phase II/III trial, patients with resected stage I NSCLC were randomized to placebo or pazopanib 800 mg/day (P800) for 6 months with a two-step Fleming design. The primary endpoint was compliance (percentage of patients receiving ≥3 months pazopanib). From the interim analysis after 64 patients were included, the IDMC recommended reducing to pazopanib 400 mg/day (P400) due to insufficient compliance, with a one-step Fleming. Although unplanned, survival data were analyzed.


RESULTS
A total of 71 patients were enrolled in each arm; 61% were male, 91% were smokers, median age was 60 years, 80% had pathological stage IA, and 16% had squamous cell carcinoma. Pazopanib compliance was 38% [95% confidence interval (CI) 23-55] with P800, increasing to 69% (95% CI 50-84; P = 0.027) with P400. Two patients had grade 4 toxicities with P800. The most common grade 3 toxicities were increased transaminases (16%), hypertension (13%), and diarrhea (9%) with P800, and gastrointestinal disorders (16%; 6% diarrhea) and hypertension (6%) with P400. Median follow-up was 47 months. Three-year recurrence-free survival was 76% (95% CI 65%-86%) with pazopanib and 83% (95% CI 74%-92%) with placebo [hazard ratio = 1.3 (95% CI 0.6-2.7), P = 0.53]. Five-year overall survival was 83% (95% CI 72-94) with pazopanib and 94% [95% CI 88-100] with placebo [hazard ratio = 1.8 (95% CI 0.6-5.5), P = 0.26].


CONCLUSIONS
In resected stage I NSCLC patients adjuvant 400 mg/day pazopanib but not 800 mg/day was feasible, although possibly infra-therapeutic and failed to improve relapse-free survival.
Department of Cancer Medicine, Gustave Roussy, Villejuif, France and Paris-Sud University, Orsay, France.
B
B
Besse
Thoracic Oncology, Hôpital Larrey, Centre Hospitalier Universitaire, Paul Sabatier University, Toulouse.
J
J
Mazières
Department of Biostatistics and Epidemiology, Gustave Roussy, Villejuif.|INSERM U1018, CESP, Université Paris-Sud, Université Paris-Saclay, Villejuif.
L
L
Ribassin-Majed
Multidisciplinary Oncology & Therapeutic Innovations Department, Aix Marseille University, Assistance Publique Hôpitaux de Marseille, Marseille.
F
F
Barlesi
Cancer, Institut de Cancérologie de l'Ouest, Nantes-Angers.
J
J
Bennouna
Department of Oncology, Centre François Baclesse, Caen.
R
R
Gervais
Pneumology, Hôpital Pasteur, Hôpitaux Civils de Colmar, Colmar.
L
L
Moreau
Pneumology, Hôpital Inter Armées Sainte-Anne, Toulon.
H
H
Berard
Respiratory Disease Department, Emile Muller Hospital, GHRMSA, Mulhouse.
D
D
Debieuvre
Respiratory Medicine Department, Hospital, Avenue Rubillard, Le Mans.
O
O
Molinier
Thoracic Oncology Unit, PTV, CHU Grenoble Alpes and INSERM U823, Grenoble.
D
D
Moro-Sibilot
Pneumology, Hopital Lyon Sud, Pierre-Bénite.
P J
PJ
Souquet
Department of Oncology, Centre de Cancérologie du Grand Montpellier, Montpellier.
S
S
Jacquot
Department of Pulmonology, Centre Hospitalier Alpes Leman, Contamine sur Arve.
L
L
Petit
Pneumology, Centre Hospitalier Universitaire, Rennes.
H
H
Lena
Department of Biostatistics and Epidemiology, Gustave Roussy, Villejuif.|INSERM U1018, CESP, Université Paris-Sud, Université Paris-Saclay, Villejuif.
J P
JP
Pignon
Department of Biostatistics and Epidemiology, Gustave Roussy, Villejuif.|INSERM U1018, CESP, Université Paris-Sud, Université Paris-Saclay, Villejuif.
B
B
Lacas
Intergroupe Francophone de Cancérologie Thoracique (IFCT), Paris.
F
F
Morin
Intergroupe Francophone de Cancérologie Thoracique (IFCT), Paris.
B
B
Milleron
Thoracic Oncology Department and Early Phase Unit CIC 1425-CLIP2 Paris-Nord, Bichat-Claude Bernard University Hospital-APHP, Paris-Diderot University, Paris.
G
G
Zalcman
Medical Oncology, Gustave Roussy, Paris-Sud University, Villejuif, France.
J C
JC
Soria
D000328:Adult; D000368:Aged; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007191:Indazoles; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D009367:Neoplasm Staging; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D011743:Pyrimidines / Q000008:administration & dosage* / Q000009:adverse effects; D013449:Sulfonamides / Q000008:administration & dosage* / Q000009:adverse effects
D007191:Indazoles; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D013449:Sulfonamides; C516667:pazopanib
adjuvant; compliance; non-small-cell lung cancer; pazopanib; randomized phase 2 trial; survival