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Phase III trial of nilotinib versus imatinib as first-line targeted therapy of advanced gastrointestinal stromal tumors (GIST).
Abstracts that were granted an exception in accordance with ASCO's Conflict of Interest Policy are designated with a caret symbol (^).
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
(HR >1 favors I)
|Median PFS, mos (95% CI)
|25.9 (19.1–NE)||29.7 (26.6–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)|
|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.
Abstracts by J. Blay:
A phase II study of a new formulation of nonpegylated liposomal doxorubicin (doxorubicin GP-pharm) as first-line treatment in patients with advanced soft-tissue sarcomas (STS) who are age 65 or older: A GEIS trial.Meeting: 2011 ASCO Annual Meeting | Abstract No: 10072Category: Sarcoma - Soft Tissue
Meeting: 2011 ASCO Annual Meeting
| Abstract No: 10071
Category: Sarcoma - Soft Tissue