147853-156

A randomized, open-label phase II study of AZD4547 (AZD) versus Paclitaxel (P) in previously treated patients with advanced gastric cancer (AGC) with Fibroblast Growth Factor Receptor 2 (FGFR2) polysomy or gene amplification (amp): SHINE study.

Category: 
Gastrointestinal (Noncolorectal) Cancer
Session Type and Session Title: 
Poster Discussion Session, Gastrointestinal (Noncolorectal) Cancer
Abstract Number: 

4014

Poster Board Number: 
Board #123
Citation: 
J Clin Oncol 33, 2015 (suppl; abstr 4014)
Author(s): 
Yung-Jue Bang, Eric Van Cutsem, Wasat Mansoor, Russell D. Petty, Yee Chao, David Cunningham, David Ferry, Donal Landers, Paul Stockman, Neil R. Smith, Catherine Geh, Elaine Kilgour; Seoul National University College of Medicine, Seoul, South Korea; Digestive Oncology, University Hospital Gasthuisberg, Leuven, Belgium; The Christie NHS Foundation Trust, Manchester, United Kingdom; University of Aberdeen, Aberdeen, Scotland; Taipei Veterans General Hospital, Taipei, Taiwan; Royal Marsden, London & Surrey, United Kingdom; New Cross Hospital, Wolverhampton, United Kingdom; AstraZeneca Oncology Innovative Medicines, Macclesfield, United Kingdom; AstraZeneca, Macclesfield, United Kingdom

Abstract Disclosures

Abstract: 

Background: The prognosis for AGC patients failing 1st line treatment is poor. FGFR2 amplification occurs in ~5-10% and polysomy in > 20% of gastric cancers (GCs). AZD is a selective FGFR1-3 inhibitor with activity in FGFR2 amplified models. SHINE assessed the efficacy and safety of AZD in AGC patients with FGFR2amplification or polysomy. Methods: Patients with disease progression after 1 prior line of therapy were assigned to FGFR2 amplified or polysomy arms and randomised to oral AZD (80mg bd, 2weeks on/1week off) or P. The primary endpoint was progression-free survival (PFS). Secondary endpoints included safety. FGFR2status confirmed by FISH testing. Exploratory biomarker analysis assessed FGFR2 gene expression by nanostring and intra-tumoral heterogeneity of FGFR2amplification by image analysis of FISH stained sections. Results: Of 960 pts enrolled, 71 patients were randomised (41 AZD arm, 30 P arm). AGC FGFR2 amp prevalence was 9%. The overall median PFS on the AZD arm was 1.8 mths vs 3.5 mths for P and for the FGFR2 amplified arm was 1.5 mths for AZD vs 2.3 months for P. Pts on AZD mostly experienced G1/G2 AEs. Most common AEs causally related to AZD were stomatitis (8 pts/20%), dry mouth (7 pts/17.5%) and RPED (6/15% pts) and fully resolved off treatment. Elevations in plasma phosphate were observed on the AZD arm during the 2 week dosing period and resolved during the 1 week off. Only 21% of FGFR2amplified tumors had elevated FGFR2 expression and Image analysis showed four out of seven tumor samples, highly amplified by FISH, were amplified in < 20% of the tumor section. Conclusions: AZD was well-tolerated. The analysis of PFS did not show any statistically significant difference in favour of the AZD arm, compared with the P arm in FGFR2 amplified or polysomy patients selected by FISH. Exploratory biomarker analysis revealed marked intra-tumor heterogeneity of FGFR2 amplification and low concordance with elevated FGFR2 expression. The observed increase in plasma phosphate provides evidence that AZD at this dose and schedule causes pharmacologic target inhibition. Clinical trial information: NCT01457846