Systemic Therapy and Future of GEJ Cancer Treatment

Manish A. Shah, MD:So, if a patient did receive second-line therapy, let’s say Taxol/Cyramza, and then after some time had progression, the question becomes, is third-line therapy an option? And I think that, again, there’s a discussion. It depends on the performance status. If a patient is having a lot of ascites, having visceral metastases, spending more time in bed than not in bed, then it’s not clear that a third-line treatment would be very beneficial, and it may be better to think about supportive care hospice. If, however, the patient is quite functional, active, and motivated to get third-line therapy, then obviously I would look for a clinical trial. But short of a trial, I would consider a third-line agent, typically irinotecan.

Closing thoughts for this case. We talked about how it’s unfortunately a typical presentation, and we talked a lot about the standard options for treatment. I might just mention that I think the options that we talked about in this interview are likely to change in the next 6 to 12 months. Drug development in gastric and GE junction cancer is quite active. Thousands of patients are in clinical trials. We’re awaiting the phase III data of the first-line regimen of FOLFOX plus or minus the MMP9 inhibitor andecaliximab. And if that study is positive, that may change options. We’re awaiting data from the first-line pembrolizumab study. The first-line nivolumab and ipilimumab phase III study is still accruing, but that may change options. And that’s just what we know about now. Just a month ago we received approval of our positive data of LONSURF in the third-line setting, so that will change options as well.

So, I think the shelf life for this interview is, fortunately, not going to be great, or actually you can invite me back, because there will be other options in the not-too-distant future.

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