Gastric Cancer: Paclitaxel/Ramucirumab vs Chemotherapy

Daniel Catenacci, MD:The rationale for using ramucirumab in the second-line setting in addition to paclitaxel, as opposed to paclitaxel alone, is based on a randomized phase III study called the RAINBOW study. That study evaluated second-line patients who had progressed on first-line fluoropyrimidine and a platinum-based regimen and were randomized to paclitaxel versus paclitaxel plus ramucirumab.

That study had a primary endpoint of overall survival, and the primary endpoint was met. The hazard ratio of benefit was around 0.8. So, the improvement absolute in overall survival is a couple of months. Therefore, this is a strategy, and has the rationale to use, to improve palliative symptoms and also duration of control.

The response rate in that study was approximately 30% to second-line therapy with paclitaxel and ramucirumab, as opposed to monotherapy paclitaxel or other taxane studies, on the border of 10% to 15%. So, again, a second-line regimen that has a higher response rate has a higher benefit rate and higher palliative rate.

The safety profile of ramucirumab is very mild. Generally, the things to watch out for would be infusion reaction in a small percentage of patients, and that can be premedicated with antihistamine and acetaminophen. The longer-term chronic toxicities would be mild also. Usually it’s symptomatic hypertension, which is essential hypertension that can be managed. And then proteinuria; also asymptomatic for the most part, which can be followed with urinalysis prior to treatments. Very rarely would there be a nephrotic syndrome in less than 2% of patients who were assessed. So generally, the toxicity of monotherapy ramucirumab is considered mild. In addition to paclitaxel in the RAINBOW study, interestingly, the mucositis rate was a little higher, and also the cytopenias, but completely manageable and in the realm of an oncologist’s repertoire of how to manage these patients.

My experience with ramucirumab in the second-line setting, either with a taxane or with a FOLFIRI regimen, has been a good one. Generally, it’s well tolerated. It doesn’t add an increased toxicity profile. We know that it improves response rates, it improves progression-free survival, and it improves overall survival. So overall, my impression and experiences have been good.

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