GEJ Cancer: Chemotherapy & Second-Line Options

Manish A. Shah, MD:Unfortunately, this patient did start with the standard 2-drug regimen of FOLFOX, or oxaliplatin and the 5-FU. He had neuropathy, so the oxaliplatin was dosage reduced and then stopped after only a few months of therapy. And I think the response was modest. He progressed a few months after that.

So, you know FOLFOX is an active regimen. I’ve had patients who have had a near-clinical CR with FOLFOX. This patient isn’t that. I think it’s a typical response, modest, but one thing that I always wonder about is whether or not we should push the oxaliplatin a little further. Instead of 4 months, try to do 6 months of therapy. These are questions we really don’t have answers to yet from our clinical trials.

Patients with gastric cancer have multiple lines of therapy options. The first-line option tends to be a doublet with oxaliplatin or cisplatin and 5-FU. Unfortunately, most patients with metastatic disease will ultimately die of their disease. The goal of treatment is to control the disease and maintain their quality of life for as long as possible. We are improving our outcomes. Not too long ago, 10 years or so, the median survival for metastatic disease was 8 to 9 months. We’re approaching a year now, and I think if a patient is able to get first-line therapy, second-line therapy, third-line therapy, it could be even longer than that. And in my practice, I have many patients who are out 2 years with metastatic disease.

So, in this patient it would be an important discussion to sort of talk about what our goals really should be. He has progressed on first-line therapy. We would talk about second-line options. Our typical option, our preference would be Taxol (paclitaxel) and Cyramza (ramucirumab), which is a VEGFR2 inhibitor. But other options exist. Irinotecan is an active option, and ramucirumab alone is an option as well.

Although those 3 options haven’t been compared head-to-head, the Taxol/Cyramza combination is indeed superior to Taxol alone. And Taxol and irinotecan and ramucirumab monotherapy all seem to have similar activity. So, these are the options, and each one has their own toxicity profile that may play a role in the decision.

The time course for a patient, I guess, can play a role in our decision for how we treat the patient. So, most patients can have disease control or response and will be on first-line therapy for longer than 6 months, maybe 8 or 9 months, and then we can switch to second-line therapy. But there is a small cohort of patients who have primary refractory disease. They have early progression, within 3 months or so. There aren’t great data for that population. We need to understand this population better. But in my experience, patients who are primary refractory, they rarely have a great response to standard second-line and third-line options. So, we really are looking for clinical trials there. We’re looking for targeted agents as well. If the patient isHER2-positive, they often would have gotten trastuzumab in the first-line setting. But if for some reason they didn’t, then that would be an obvious go-to choice. But we don’t really have great evidence-based data on what to do beyond our standard options, which are honestly not that great for patients with primary refractory disease.

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