GEJ Cancer: Paclitaxel/Ramucirumab and Supportive Care

Manish A. Shah, MD:So, let’s talk about paclitaxel and ramucirumab in some detail. There was a phase III study that compared the combination of paclitaxel/ramucirumab with paclitaxel alone. And the combination did improve survival. The hazard ratio was around 0.8. So, it’s 20% improvement in survival with the combination therapy.

Ramucirumab is a VEGFR2 antibody inhibitor. That toxicity profile of ramucirumab is similar to what we see with bevacizumab. So, hypertension and some bleeding risk—that’s what we saw on the study as well. We really didn’t see a significant increase in perforation, which you did see with bevacizumab in the earlier studies. And we do see a little bit more lymphopenia with Taxol/ramucirumab versus Taxol alone. But generally, the combination is pretty well tolerated with minimal added toxicity over what you see with Taxol alone.

The one thing you might consider is that for patients who have significant neuropathy, you might need to question whether Taxol is the right choice. So, single-agent ramucirumab might be considered. Irinotecan might be considered. There are limited data combining those 2, although theoretically there really shouldn’t be any problem with that. The FOLFIRI/bevacizumab option, for example, was really quite active. And in terms of the efficacy, I mentioned the 20% improvement in survival. The response rates are about 20% with the combination. Ramucirumab has really no response by itself, but there is synergy when you combine them.

Supportive care is the key aspect of managing anybody with gastric and GE junction cancer. So, are often issues of nutrition, neuropathy, and also social issues related to depression or anxiety, coping, things like that. And that often requires counseling regularly during our visits. Often patients could seek help from a social worker or group therapy sessions for that. From a nutrition standpoint, seeing a dietitian is important, but sometimes we do need to place a stent for proximal obstructions. Sometimes radiation is helpful. Sometimes a feeding tube is necessary.

In terms of the neuropathy, there are medications that can help mitigate the symptoms of neuropathy. We commonly use gabapentin, Cymbalta (duloxetine), and Lyrica (pregabalin). Alpha lipoic acid can help. But there isn’t a great magic bullet for that. Those are, I think, the most prevalent supportive care issues, but many others exist.

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