Approach to Unresectable Stage 4 Gastric Adenocarcinoma - Episode 5
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