Phase II study of sunitinib as second-line treatment for advanced gastric cancer

Abstract

Purpose: This phase II, open-label, multicenter study assessed the oral, multitargeted, tyrosine kinase inhibitor sunitinib in patients with advanced gastric or gastroesophageal junction adenocarcinoma who had received prior chemotherapy.

Experimental design: Patients received sunitinib 50 mg/day on Schedule 4/2 (4 weeks on treatment, followed by 2 weeks off treatment). The primary endpoint was objective response rate; secondary endpoints included clinical benefit rate, duration of response, progression-free survival (PFS), overall survival (OS), pharmacokinetics, pharmacodynamics, safety and tolerability, and quality of life.

Results: Of 78 patients enrolled, most had gastric adenocarcinoma (93.6%) and metastatic disease (93.6%). All were evaluable for safety and efficacy. Two patients (2.6%) had partial responses and 25 patients (32.1%) had a best response of stable disease for ≥6 weeks. Median PFS was 2.3 months (95% confidence interval [CI], 1.6-2.6 months) and median OS was 6.8 months (95% CI, 4.4-9.6 months). Grade ≥ 3 thrombocytopenia and neutropenia were reported in 34.6% and 29.4% of patients, respectively, and the most common non-hematologic adverse events were fatigue, anorexia, nausea, diarrhea, and stomatitis. Pharmacokinetics of sunitinib and its active metabolite were consistent with previous reports. There were no marked associations between baseline soluble protein levels, or changes from baseline, and measures of clinical outcome.

Conclusions: The progression-delaying effect and manageable toxicity observed with sunitinib in this study suggest that although single-agent sunitinib has insufficient clinical value as second-line treatment for advanced gastric cancer, its role in combination with chemotherapy merits further study.

Fig. 1

Patient disposition. ITT, intention-to-treat. RECIST, Response Evaluation Criteria in Solid Tumors

Fig. 2

Kaplan-Meier curve of a progression-free survival and b overall survival following treatment with sunitinib 50 mg/day on Schedule 4/2

Fig. 3

Total drug (sunitinib + SU12662) dose-corrected (reference dose: 50 mg) plasma trough concentration versus cycle/day box plot. Box boundaries denote 25th and 75th percentiles; lines within the box show the median value and expected range of the median. Whiskers indicate the minimum and maximum data values; where outliers are present (asterisks), whiskers extend to a maximum of 1.5 times the interquartile range