Treatment of Relapsed Metastatic Colorectal Cancer

Tanios Bekaii-Saab, MD, FACP:The patient did fairly well on cetuximab maintenance and, in fact, continued on it until August 2016. The patient started to complain of more symptoms—weight loss, fatigue, nausea. And then, a CT scan of the chest, abdomen, and pelvis done at the time showed progressive disease both in the lungs, and now there were some new spots in the liver. So, the question is, what do you do?

There are 2 options, frankly. You have the option of reinstituting the FOLFIRI or switching to CapeOx/bevacizumab. The decision was to proceed with CapeOx/bevacizumab. That came through a discussion with her physician. At that time, her blood pressure seemed to be well controlled and continued to be well controlled on CapeOx/bevacizumab. And after 2 months, the patient had stable disease. After 4 months, it was the same, and so she continued with CapeOx/bevacizumab for another 4 months. At 4 months, the decision was made to drop oxaliplatin and continue with capecitabine and bevacizumab. So, this patient progressed on FOLFIRI plus cetuximab. The first question that comes to mind is, do you reinstate FOLFIRI? Because technically, it has taken many months before she actually progressed, and so she could still be sensitive to FOLFIRI. So, that’s one option. The other option, which I think is a very logical option, is to switch both the chemotherapy backbone and the biologic. My own preference would probably be to institute FOLFIRI first and continue with cetuximab. And then, after the progression on FOLFIRI/cetuximab, then I would go CapeOx/bevacizumab. But as I said, both options are very reasonable.

CapeOx, or FOLFOX, would be the next option after failure of FOLFIRI, and then the switch of the biologic as well. The most important question, given the best medical history of this patient, is, should we give bevacizumab? We know bevacizumab increases the risk of arterial thrombolic events, like strokes, heart attacks, even increases the risk of uncontrolled hypertension. This patient has controlled hypertension, and it’s being controlled on just 1 drug and for quite a while. She also had coronary artery disease that had angioplasty 4 to 5 years prior, so the decision was made whether to institute bevacizumab or not. And typically, 6 to 12 months is a comfort zone. And since that patient had years of symptom-free coronary artery disease, seems to be well controlled, I think it would make sense to place her on an anti-VEGF agent, specifically, bevacizumab.

Now, of course, we have 3 agents available on the market: ramucirumab, ziv-aflibercept, and bevacizumab. And all 3 agents seem to induce a very similar benefit when given in the second-line setting. There doesn’t seem to be one that stands out versus the other, except one is more expensive: ramucirumab. Ziv-aflibercept seems to be a little bit more toxic. And in fact, for most patients, we’re very used to bevacizumab and that would end up being the default.

If you look at the NCCN guidelines, all 3 are listed. However, bevacizumab is preferred for the specific reason that it doesn’t make sense to have 3 of the same that may be more expensive, more toxic, and we’re less familiar with. So, for that purpose, we’d go with bevacizumab. This is a patient who has isolated disease both in the lung and the liver, or that’s isolated to the lung and isolated to the liver, that’s actually pretty extensive because of 2 organs being involved. Nonetheless, there’s always this, and should always be, discussion: could we address the local disease first? And the answer is, in the patient that has metastatic disease, localized approaches do not make sense. Thus, this patient, at this point, would not be eligible for any localized approaches, just systemic approaches with chemotherapy plus bevacizumab.

Transcript edited for clarity.

October 2015

• A 64-year-old woman underwent left hemicolectomy for an obstructing mass at the rectosigmoid junction
  • CEA were elevated, 23.3 ng/mL
  • Pathology showed an undifferentiated adenocarcinoma, invading through the muscularis mucosae up to the pericolic fat; 14 nodes were biopsied, 10 of which were metastatic
  • Imaging with PET/CT showed several lung lesions, three measuring up to 3.0 cm in size
  • Mutational status was both RAS and BRAF wild-type
  • Microsatellite stable
  • Diagnosis; high grade colorectal adenocarcinoma, stage T4N2M1
• PMH includes arterial hypertension, well-controlled on an ACE inhibitor and coronary angioplasty with stent placement 4 years ago
• The patient received systemic therapy with FOLFIRI + cetuximab; grade 1 rash and grade 2 thrombocytopenia were managed with dose adjustment of FOLFIRI
• Follow-up imaging at 2 months and 4 months showed significant response in the lung lesions
• The patient was continued on maintenance therapy with cetuximab

August 2016

• The patient complains of weight loss, nausea and fatigue
• CT of the chest, abdomen, and pelvis showed marked progression in 2 of the lung lesions and development of new liver lesions
• The patient was switched to CAPEOX with bevacizumab. Her blood pressure was closely monitored and remained stable
• Follow up imaging at 2 months and at 4 months showed stable disease in the lung and liver lesions and improvement of her symptoms
• At 4 months, oxaliplatin was discontinued; maintenance therapy with capecitabine and bevacizumab was continued

January 2017

• At 5 months, the patient reports having reappearance of her symptoms, although she continues her normal physical activity
• CEA level is rising significantly
• Follow up CT showed further progressive disease in the lung and the appearance of several small boney lesions
• The patient is motivated to try another therapy and has opted for regorafenib