Pazopanib with 5-FU and oxaliplatin as first line therapy in advanced gastric cancer: a randomized phase-II study - the PaFLO trial. A study of the Arbeitsgemeinschaft Internistische Onkologie AIO-STO-0510
Mené en Allemagne sur 78 patients atteints d'un cancer de l'estomac ou de la jonction oesogastrique de stade avancé, cet essai de phase II évalue l'efficacité, du point de vue de la survie sans progression à 6 mois, et la toxicité de l'ajout du pazopanib à un traitement de première ligne combinant 5-fluorouracile et oxaliplatine
VEGF inhibition in gastric cancer has a proven benefit in the second line setting [1–3]. Pazopanib, an oral tyrosine kinase inhibitor, selectively inhibits VEGFR-1, −2 and − 3, c-kit and PDGF-R resulting in inhibition of angiogenesis. This open-label randomized phase II trial (2:1) investigated the efficacy of combining pazopanib with FLO (5-fluorouracil, Oxaliplatin) vs FLO alone (internal control arm) as first-line treatment in patients (pts) with advanced adenocarcinoma of the stomach and gastro-esophageal junction (GEJ). 87 pts were randomized and 78 pts were eligible and evaluable (PaFLO arm 51 pts, FLO arm 27 pts). The PFS rate at 6 mhs (primary endpoint) was 34% in the PaFLO arm vs 30% in the FLO arm. Comparing PaFLO with FLO median PFS was 4.66 mths (95% CI 2.87-6.46) vs 4.47 mths (95% CI 1.79-7.14) (95% CI, HR 0.96 (0.60-1.55), P = 0.882 (exploratory)); median OS was 10.19 mths (95% CI 5.46-14.92) vs 7.33 mths (95% CI 4.93-9.73), (95% CI HR 1.01 [0.62-1.65], P = 0.953, exploratory), disease control rate was 72% vs 59%. PaFLO was well tolerable, toxicities were slightly higher in the PaFLO arm. Major adverse events were loss of appetite, nausea, fatigue, diarrhea, neutropenia and thrombocytopenia. Adding pazopanib to chemotherapy shows signs of efficacy but no major improvement in this randomized phase 2 trial. The PFS at 6 months in both arms were lower than expected from the literature. Biomarkers identifying subgroups who benefit and novel combinations are needed. ClinicalTrials.gov: NCT01503372. This article is protected by copyright. All rights reserved.