Goals of Second-Line Therapy in Stage 4 Gastric Cancer

Daniel Catenacci, MD:The goal of therapy in the second-line setting is very similar to the goal in the first-line setting. That is, to palliate symptoms and to improve survival time as long as possible while limiting toxicity of the treatments. In the second-line setting, there are, again, several regimens to choose from. One of the most common regimens, and an emerging second-line standard, would be paclitaxel with ramucirumab, which is what this patient received. Occasionally, because patients in the first-line setting who are receiving oxaliplatin have residual neuropathy, sometimes using another taxane in the second line, another neurotoxic regimen, is not possible. And so, in those settings, we often use a non-neurotoxic regimen with irinotecan. A preference at our site is to use FOLFIRI.

We do include ramucirumab with paclitaxel, as per the RAINBOW study. In the setting where we do not use a taxane but instead use FOLFIRI, for those patients we would still add ramucirumab. There is some retrospective data in preparation to be published, and also there’s a large phase III study that’s ongoing in Europe assessing a second-line therapy with FOLFIRI and ramucirumab. FOLFIRI and ramucirumab, of course, are approved as a standard option in the second-line setting in colon cancer. And so, safety and tolerability are already established; it’s just efficacy in the second-line setting of gastric cancer that is not.

In terms of patients who have rapid progression within the first 6 months of first-line therapy with FOLFOX, it doesn’t necessarily change our strategy in terms of what we would do in the second-line setting. We do know that those patients tend to do worse overall. Patients who are responding to first-line therapy and last longer on first-line therapy tend to do better overall, regardless. At second line, if a patient is still eligible for second-line therapy and may have preserved performance status, we would still proceed accordingly with the appropriate standard second-line options.

Transcript edited for clarity.

A 61-Year-Old Woman With Stage 4 Gastric Cancer

November 2017

• A 61-year-old Hispanic woman presents to her PCP complaining of unexplained weight loss (15 lbs over 6 months), intermittent abdominal pain, fatigue, and recent onset of vomiting
• BMI: 23
• PE: negative for ascites
• Notable laboratory findings:
  • HB: 11.2 g/dL
  • LFT: WNL
  • GFR: 100
  • CEA, 18.4 ng/mL
  • AFP, CA 19-9, and CA 125: WNL
• Upper gastric endoscopy: suspicious 7.2-cm ulcerative lesion involving the pyloric region
• Endoscopic ultrasound: suspicious lymph node
• Biopsy: confirmed poorly differentiated, gastric adenocarcinoma, diffuse histologic subtype; positive lymph node
• Molecular testing: HER2(-), MSI-stable, PD-L1 expression 0%
• CT of chest, abdomen, and pelvis: showed diffuse invasion of the gastric wall and visceral peritoneum, lymph node involvement, 1 hepatic lesion
• Staging: stage IV gastric adenocarcinoma, unresectable
• ECOG PS 0

January 2018

• The patient was started on fluorouracil and oxaliplatin (FOLFOX)
• Follow up CT at 3 months showed a response to systemic therapy

July 2018

• Patient reports increasing nausea, fatigue, and shortness of breath
• CT imaging at 7 months shows metastatic spread to multiple suprapyloric nodes and a new liver lesion
• LFT: mildly elevated; GFR: WNL; HB: 10.8 g/dL
• ECOG PS 1
• Patient is motivated to try another systemic therapy
• Treatment with paclitaxel/ramucirumab is planned