Phase II trial of nilotinib as third-line therapy for gastrointestinal stromal tumor (GIST) patients in Japan.

Abstract

10015 Background: Patients with GIST resistant to both imatinib (IM) and sunitinib (SU) have a poor prognosis and few therapeutic options. The objective of this study is to investigate efficacy and safety of nilotinib as a third line therapy for Japanese GIST pts who have shown resistance and/or intolerance to imatinib and sunitinib. Methods: A single arm, open-label trial was conducted in 8 hospitals in Japan. The key eligibility criteria included histologically confirmed KIT-positive GIST and progression on or intolerance to both imatinib and sunitinib treatment. Pts were treated with nilotinib 400 mg b.i.d. The primary endpoint was disease control rate defined as rates of CR + PR + SD (lasting at least 24 weeks) assessed by central reviewers based on RECIST criteria. Registered with Clinical Trials.gov, number NCT00718562 and sponsored by Novartis Pharmaceuticals. Results: Among the 35 pts enrolled between Sep 2008 and Apr 2009, 26 (74.3%) were resistant to both IM and SU, 6 (17.1%) IM-resistant and SU-intolerant, 2 (5.7%) IM- intolerant and SU-resistant, and the remaining 1 (2.9%) intolerant to both. The median prior maximum doses were 400 mg (≥600 mg for 16/35 pts) for IM and 50 mg (50 mg for 34/35 pts) for SU. The median age was 57 years (range 26 - 76) and 22 (62.9%) pts were male. The most common primary sites of GIST were the small intestine (21 [60.0%] pts) and stomach (11 [31.4%] pts). The median exposure to nilotinib was 120 days (range 5-316) at the time of data cut-off (02Oct2009). Disease control rate at 24 weeks was 28.6% (90% CI ; [16.4%, 43.6%]). The median PFS was 113 days. The median OS was 310 days. The objective response rate was obtained for 2.9% with 1 PR pt who carried GIST with KIT mutations in exon 11 (dup 567 - 576) and exon 17 (D820G) after resistance to both imatinib and sunitinib, and 23 pts (65.7%) had SD as the best response. Nilotinib was well tolerated; the most common treatment-related AEs of any grade were nausea, vomiting, hyperbilirubinemia and appetite loss (28.6% each). No patients developed grade 3-4 hematological toxicities except for anemia (5.7%). Conclusions: These results suggest that nilotinib is effective in Japanese GIST pts who failed both imatinib and sunitinib and well tolerated. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Chugai Pharmaceutical, Novartis, Pfizer, sanofi-aventis Tsumura Co. Daiichi Sankyo, Kyowa Hakko Kirin, Novartis, Taiho Pharmaceutical, Wyeth, Yakult Honsha