Impressions of a Case of Stage 4 GEJ Cancer

Manish A. Shah, MD:This is a case of an advanced gastric cancer. The patient presented with about a 10-lb weight loss. He underwent an endoscopy. He was found to have a cardia tumor. Imaging showed metastatic disease to the liver. They were biopsied and confirmed to be metastatic adenocarcinoma, and he started on first-line therapy. He did have a molecular profile that showed that he was HER2-negative, PD-L1—negative, and mismatch repair–deficient, which is unfortunately too frequent, all these being negative. He had initial response to therapy but then progressed, and he’s now ready for second-line therapy.

My initial impressions of this case are that, unfortunately, this is really quite typical. The patients typically present with metastatic disease. It really is a silent killer. Patients don’t have symptoms of the disease, or their symptoms are vague, and they don’t present immediately with these symptoms. Often the weight loss is felt to be intentional, and so the initial weight loss may be even felt to be a good thing. People have abdominal pain, reflux for a long time, and so it often takes time for patients to actually get to medical attention. The prodrome for gastric cancer, unfortunately, is 9 to 12 months. So, that means from the initial symptom that progressed or persisted leading to evaluation and diagnosis often is delayed 9 to 12 months. So, that’s one aspect of it.

The other aspect is that his molecular profile was in fact negative for many targeted therapies. So, he was HER2-negative, and that’s true in about 80% of patients. He was PD-L1-negative; that’s true in about 60% of patients. And he was mismatch repair deficient. That’s true in about 80% of patients.

So, as you see, most patients were actually negative for that molecular profile. Although ramucirumab is a targeted agent that we’ll discuss, the other targeted agents available in this disease—trastuzumab and pembrolizumab—won’t be available to him at this time. And then I guess the other aspect of the case is that it’s common to start with a platinum 5-FU in the beginning. And then neuropathy does happen. So, his course is actually, unfortunately, quite typical.

Transcript edited for clarity.

A 54-Year-Old Man With Stage IV Gastroesophageal Junction Cancer

January 2018

• A 54-year-old man presented to his PCP complaining of loss of appetite, indigestion, and dysphagia lasting approximately 4 months and subsequent 12-lb weight loss
• PE: patient was pale-appearing; abdominal auscultation
• Notable laboratory findings:
  • HB 10.8 g/dL
  • LFT WNL
  • CEA, 18.4 ng/mL
• Upper GI endoscopy with endoscopic ultrasound showed a hypoechoic mass, approximately 3.3 cm, located in the gastric cardia and extending to the gastroesophageal junction, infiltrating the gastric wall into the subserosal mucosa
• Biopsy results confirmed poorly differentiated gastric adenocarcinoma
  • Molecular testing; HER2(-), MSI-stable, PD-L1 expression 0%
• CT of chest, abdomen, and pelvis indicated liver mets confirmed
• Staging; GEJ adenocarcinoma T4bN0M1, unresectable, Siewert II
• PS; ECOG 0
• After multidisciplinary assessment, the patient was started on FOLFOX
• Three-month follow-up
  • Imaging showed a partial response to systemic therapy
  • Patient complained of mild neuropathy; oxaliplatin was discontinued after 4 cycles of chemotherapy

July 2018

• Patient reports increasing fatigue
• CT imaging at 6 months shows metastatic spread to multiple subcarinal and right hilar lymph nodes; increased size in two of the liver lesions
• PS; ECOG 1
• Patient is motivated to try another systemic therapy
• The patient is planned to start therapy with paclitaxel/ramucirumab