Abstract P6-11-03: A phase 2 open-label study of lucitanib in patients (pts) with FGF aberrant metastatic breast cancer (MBC)
Authors: Mayer IA , Arteaga CL , Nanda R , Miller KD , Jhaveri K , Brufsky AM , Rugo H , Yardley DA , Vahdat LT , Sadeghi S , Audeh MW , Rolfe L , Litten J , Knox A , Raponi M , Tankersley C , Isaacson J , Wride K , Morganstern DE , Vogel C , Connolly RM , Gradishar WJ , Patel R , Pusztai L , Abu-Khalaf M 
Published: March 2017

BACKGROUND: Lucitanib is a potent, oral antiangiogenic tyrosine kinase inhibitor of Vascular Endothelial Growth Factor Receptors 1-3 (VEGFR1-3), Platelet-Derived Growth Factor Receptors alpha and beta (PDGFRα/β), and Fibroblast Growth Factor Receptors 1-3 (FGFR1-3). FGF aberrancies (amplification of FGFR1,or 11q[amplicon containing FGF ligands 3, 4, and 19]), are genomic alterations observed in over 20% of breast cancer pts and promote cancer proliferation and survival.

METHODS: MBC pts who had received at least 1 metastatic line of therapy were randomized 1:1 to 10 or 15 mg QD of lucitanib. Stratification was based on local assessment of FGF aberrancy; pts with both FGFR1 and 11q-amplified tumors were stratified as FGFR1 amplified. Central confirmation of FGFR1 or 11q amplification was done using Abbott FISH probes (FGFR1 or 11q copy number ≥ 6 and a ratio of FGFR1 or 11q to centromere ≥ 2). Investigator-assessed progression-free survival (PFS) was the primary endpoint. Secondary endpoints included objective response rate (ORR) per RECIST 1.1, disease control rate (DCR), duration of response (DR), and incidence of treatment-emergent adverse events (TEAE).

RESULTS: Enrollment completed in 3/2016; 178 pts that received at least 1 dose of lucitanib are included in this analysis (baseline characteristics in Table 1). Due to grade 3 hypertension in the 15 mg group (46% vs 37% in 10 mg group), enrollment to the 15 mg group was halted. Overall, most pts (97%) experienced at least 1 TEAE, with the most frequently (≥ 30%) occurring events being hypertension (73%), fatigue (48%), nausea (43%), hypothyroidism (40%), and headache (33%). Grade ≥ 3 TEAEs occurred in 66% of pts, with hypertension as the most frequent event (40%) followed by proteinuria and hyponatremia (both 6%). AEs were manageable with dose interruption or reduction, with approximately 8% of pts ending treatment due to an AE. Current median PFS is 3.5 mos (95% CI 2.8-4.6; range 0.62-12.95) and 2.6 mos (95% CI 1.8-2.9; range 0.82-18.87) respectively for the 10 mg and 15 mg treatment groups. No differences in clinical activity were observed by treatment group, FGF aberrancy, hormone receptor or HER2 status. Of the 168 evaluable pts, confirmed ORR was 3%; overall DCR was 27% (32% for pts in the 10 mg group compared to 20% for the 15 mg group); overall mean (standard deviation) DR of 3.3 (1.8) mos.

Baseline Characteristics 10 mg QD15 mg QD N=109N=69Age (years)Median5653Range27-8227-80SexFemale109 (100%)67 (97%)Male02 (3%)ECOG PSmissing5 (5%)2 (3%)051 (47%)30 (43%)153 (49%)37 (54%)Number of prior anticancer therapies in the metastatic setting&gt; 332 (29%)21 (30%)3-648 (44%)32 (46%)&gt; 629 (27%)16 (23%)Endocrine/HER2 statusmissing7 (6%)1 (1%)ER+ or PR+74 (68%)50 (73%)HER2+12 (11%)7 (10%)TNBC16 (15%)11 (16%)FGFR aberrancyFGFR1 amplified54 (49%)29 (42%)11q amplified31 (28%)24 (35%)FGFR1 and 11q amplified13 (12%)9 (13%)FGFR1 and 11q non-amplified11 (10%)7 (10%)

CONCLUSION: At 10 mg QD, lucitanib has modest activity with manageable toxicity in this heavily pretreated pt population. Future clinical development for lucitanib may focus on alternative biomarkers to identify sensitive tumors and rational combinations with other anti-cancer drugs.

Citation Format: Mayer IA, Arteaga CL, Nanda R, Miller KD, Jhaveri K, Brufsky AM, Rugo H, Yardley DA, Vahdat LT, Sadeghi S, Audeh MW, Rolfe L, Litten J, Knox A, Raponi M, Tankersley C, Isaacson J, Wride K, Morganstern DE, Vogel C, Connolly RM, Gradishar WJ, Patel R, Pusztai L, Abu-Khalaf M. A phase 2 open-label study of lucitanib in patients (pts) with FGF aberrant metastatic breast cancer (MBC) [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P6-11-03.