Phase III trial of nilotinib versus imatinib as first-line targeted therapy of advanced gastrointestinal stromal tumors (GIST).

Session Type and Session Title: 
Oral Abstract Session, Sarcoma
Abstract Number: 
J Clin Oncol 31, 2013 (suppl; abstr 10501^)
Jean-Yves Blay, Lin Shen, Yoon-Koo Kang, Piotr Rutkowski, Shukui Qin, Dmitry Nosov, Steven C. Novick, Lilia Taningco, Shuyuan Mo, Peter Reichardt, George D. Demetri; University Claude Bernard Lyon I, Centre Léon Bérard, Lyon, France; Department of Gastrointestinal Oncology, Key laboratory of Carcinogenesis & Translational Research under Ministry of Education, Peking University Cancer Hospital, Beijing, China; Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea; Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland; No. 81 Hospital of PLA, Nanjing, China; Blokhin Oncology Research Center, Moscow, Russia; Novartis Pharmaceuticals Corp, East Hanover, NJ; Novartis Pharmaceuticals, Oncology, Florham Park, NJ; HELIOS Klinikum Bad Saarow, Bad Saarow, Germany; Dana-Farber Cancer Institute/Harvard Medical School, Boston, MA

Abstracts that were granted an exception in accordance with ASCO's Conflict of Interest Policy are designated with a caret symbol (^).

Abstract Disclosures


Background: Nilotinib (N) is a Bcr-Abl, KIT, and PDGFR tyrosine kinase inhibitor. This Phase III trial compared N and imatinib (I) as first-line therapy of advanced GIST. Accrual was stopped when a futility boundary was crossed at interim analysis (IA). This final analysis of the core study examined the effect of mutation on outcomes. Methods: Patients (pts) with unresectable and/or metastatic GIST who had no prior antineoplastic therapy or had recurrence ≥6 months (mos) after adjuvant I were randomized 1:1 to open-label N 400 mg bid or I 400 mg qd (400 mg bid for KIT exon 9 mutants). The primary endpoint was progression-free survival (PFS) per adjudicated central review. Enrollment targeted 736 pts to observe 375 events, yielding 90% power to detect a hazard ratio (HR) of 0.71 (median, 28 [N] and 20 [I] mos) with two-sided 5% type I error. Prior to IA, crossover was allowed only for pts with progressive disease (PD); after IA, pts on N with or without PD were offered I. Results: At IA, the PFS HR for N vs I of >1.111 suggested a low probability of N superiority to I. Final analysis was performed in 644 pts; both PFS and OS favored I. In subgroup analysis of 401 pts who had mutational data, there was a large PFS difference favoring I in KIT exon 9 mutants, but similar PFS in KIT exon 11 mutants (Table). Based on immature data, OS favored I in all mutants. Conclusions: The IA showed N could not be superior to I for PFS in the overall population as first-line targeted therapy for pts with advanced GIST. PFS of N and I differed according to molecular subtypes, with PFSfavoring Iin KIT exon 9 mutants but roughly similar in exon 11 mutants. Clinical trial information: NCT00785785.

Nilotinib (n=324) Imatinib (n=320) HR (95% confidence
interval [CI])
(HR >1 favors I)
Median PFS, mos (95% CI)
25.9 (19.1–NE) 29.7 (26.6–NE)
KIT mutant
Exon 11 NE
32.3 (29.7–NE)
Exon 9 3.0 (2.8–3.2)
24 mos PFS, % (95% CI)
51.6 (43.0–59.5) 59.2 (50.9–66.5) 1.466 (1.104–1.945)
KIT mutant
Exon 11 69.6 (57.6–78.8) 67.5 (55.9–76.7) 1.120 (0.683–1.836)
Exon 9 NEa 67.1 (39.9–84.1) 32.456 (7.113–148.088)
24 mos OS, % (95% CI)
81.8 (76.6–86.0) 90.0 (85.9–93.0) 1.850 (1.198–2.857)

NE, nonestimable. aAll exon 9 mutants on N had a PFS event or censoring within 6 mos.