6533b86efe1ef96bd12cc8f9

RESEARCH PRODUCT

FOLFIRI plus sunitinib versus FOLFIRI alone in advanced chemorefractory esophagogastric cancer patients: A randomized placebo-controlled multicentric AIO phase II trial

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4086 Background: Sunitinib is an receptor tyrosine kinase (RTK) inhibitor of VEGFR1-3, PDGFR-α-β, and other RTK. After we established Sunitinib (Sun) alone associated with limited response rate (RR) and good tolerability in refractory advanced esophagogastric cancer patients (Moehler et al. EUR J Cancer. 2011, 47: 1511), this double-blinded placebo-controlled phase II evaluated safety and efficacy of SUN as add-on in second-line or third-line FOLFIRI (ClinicalTrials.gov NCT01020630). Methods: Patients with failure of any prior docetaxel and/or platinum-based chemotherapy were randomized to receive 6-week cycles including FOLFIRI two weekly and SUN (25 mg) versus (vs) placebo (PLA) daily for 4 consecutive weeks followed by a 2-week rest. Primary endpoint was progression-free survival (PFS). Results: 91 randomized patients (ITT) had similar characteristics in both groups (SUN/PLA 45/46). Both groups had 2.7 treatment cycles. Objective RR was 20/29%, and tumor control rate was 58/56 % for SUN/PLA, respectively. Median PFS was similar for SUN vs. PLA with 3.6 vs. 3.3 months, respectively (HR 1.11; 95%CI 0.70-1.74, P = 0.66). Median overall survival (OS) was longer for SUN vs. PLA with 10.5 vs. 9.0 months, in ITT (HR 0.816; 95%CI 0.50 - 1.34, P = 0.42, one-sided 0.21) and in the per protocol population (HR 0.71; 95%CI 0.41 - 1.24, P = 0.23) respectively. No unexpected higher toxicities, SAE or SUSAR occurred with SUN. For SUN/PLA, all grade AEs (%) possibly related to study drug were nausea 49/47%, fatigue 36/29%, vomiting 27/29%, diarrhoea 36/38%, neutropenia 62/22%, stomatitis 27/20%, and palmar-plantar erythrodysaesthesia 13/3%, and Grade 3+ AEs (%) were neutropenia 56/20%, diarrhoea 2/13%, nausea 7/7%, fatigue 0/9% and pain 0/9%, respectively. Performed quality of life outcomes were mostly in favor of Sunitinib. Conclusions: In our phase II trial, Sunitinib added to FOLFIRI increased hematotoxicity and did not improve response rates or PFS in chemotherapy-resistant GC patients. Since the regimen was safe and patients had a trend to better OS, biomarker analyses will be performed to identify subgroups that benefit from add-on Sunitinib. Clinical trial information: NCT01020630.