Gastric Adenocarcinoma

Introduction

• Virtual Molecular Tumor Board
• Patient: Gastric Adenocarcinoma
• Levine Cancer Institute
• Presented by: Dr. Jimmy Hwang

History

• Presented in summer of 2015 with back pain, malaise
• On evaluation, found to have Tbili 6.3, ALT 534, AST 238 (normal in 2014)
• RUQ U/S showed fatty infiltration, but no masses
• MRI of abdomen demonstrated intrahepatic, extrahepatic biliary ductal dilatation, with stricture in proximal common bile duct; multiple peripancreatic, celiac, portocaval LN up to 2.6 cm, and lobulated enhancing appearance to proximal stomach wall, measuring up to 5 cm.
• EGD demonstrated a large, submucosal noncircumferential mass at the GEJ/gastric cardia.
  • Biopsy demonstrated adenocarcinoma, intestinal type
  • HER2 amplified (HER-2: CEP17 ratio of 4.8)
• PET/CT demonstrated hypermetabolic soft tissue thickening in the GEJ and cardia, measuring up to 40 mm; multiple hypermetabolic pulmonary nodules up to 1.6 cm, and hypermetabolic mediastinal, bilateral hilar, retroperitoneal/paraortic and peripancreatic LN; hypermetabolic 24 mm right adrenal lesion

Pathology: HER 2+ positivity by IHC

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Molecular Tumor Summary

• Adenocarcinoma, moderately to poorly differentiated, intestinal type
• HER2 amplified (HER2: CEP17 ratio=4.8)

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HER-2 in Gastric/GEJ Adenocarcinoma: TOGA

• Bang et al, Lancet 2010; 376: 687-697
• 594 pts with advanced/metastatic HER2+ gastric/gastroesophageal adenocarcinoma, no prior chemo for metastatic disease enrolled 9/2005-12/2008:
  • Primary endpoint: Survival
  • Stratified by disease extent, primary site, measurable disease, PS, fluoropyrimidine
• Cisplatin + capecitabine (or 5FU in about 12% of pts) q 3 weeks x 6 cycles, +/- trastuzumab (8 mg/kg IV D#1, then 6 mg/kg q 3 weeks)

HER-2 in Gastric, GEJ Cancers

• Bang, ASCO 2009, #4556
• FISH or :HercepTest 3+: Overall 22.1% positiveM
• By location: Stomach: 20.9%, GEJ 33.2%
• By Lauren class: Intestinal type: 32.2%, diffuse type: 6.1%
• By Country: wide variation, no clear pattern
• Similar to other studies (8-23% by HercepTest)

Gastric Cancer: TOGA: Survival

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Gastric Cancer: TOGA Outcomes

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Treatment History

• FOLFOX/trastuzumab
  • After 2 months, essentially stable disease, some decrease in thickening of GE junction, perhaps slight decrease in lung, LN. Symptomatic improvement in pain
  • After 4 months, progressive disease with new liver lesions, lung lesions and some increase in prior lung lesions
• Paclitaxel/trastuzumab
  • After two months of therapy, mixed response with response in lungs, but increase in size (but not number) of liver metastases
• Paclitaxel/ramucirumab
  • After two months of therapy, increase in lymphadenopathy, and slightly in the lungs, but liver was stable
• Irinotecan/trastuzumab (MDACC recommended FOLFIRI): Ongoing

Discussion

• In patients with HER2 amplified/overexpressing disease, antiHER2 therapy with trastuzumab in combination with chemotherapy improves outcomes
• It is less clear whether continuing antiHER2 therapy after initial progression continues to benefit patients