Emerging Targeted Therapies in the Treatment of Advanced or Metastatic Esophagogastric Cancer (EGC)

Abstract

Esophagogastric cancer (EGC) is the 2nd leading cause of cancer-related death worldwide and have unmet need to explore new treatment options. In first phase II study Heat Shock Protein (HSP 90) inhibitor Ganetespib show common grade 3/4 AEs leucopenia (12%), fatigue (12%), diarrhea (8%), and elevated ALKP (8%). The ORR of 4% reflects the single patient of 26 who had a complete response. Median PFS and OS was 61 days, 94 days respectively.Study was terminated early due to insufficient evidence of single-agent activity. Manageable toxicity,durable CR and 2 minor responses suggest that there may be a subset of EG patients who could benefit from this drug. In the 2nd study we explored the clinicopathological features and outcome of patients with MET amplified EGC. METamp was seen in 28 (12%) of patients versus 205 (88%) patients without amplification. Of MET-amplified patients, 7 (25%) had a TP53 mutation, 5 (18%) had HER2 co-amplification, and 1 (3.6%) had a PIK3CA mutation. Progression-free survival to initial treatment for MET-amplified patients were (5.6 vs 9.1 months, p=0.013) and for those with metastatic disease at presentation (4.4 vs 7.9 months, p=0.035). Overall, patients with MET amplification had shorter overall survival (15.3 vs 24.6 months, p=0.014).