Factors to Consider for Left-Sided Metastatic CRC

Tanios Bekaii-Saab, MD:So, that’s a 64-year-old woman who presented initially with an obstructive mass on the left side, underwent a colonoscopy, and got biopsied, and her tumor was found to be consistent with adenocarcinoma with colon primary—RAS wild-type, BRAF wild-type, and microsatellite stable. Unfortunately, when she got staged, she had a CT scan and a PET/CT, which suggested multiple bilateral lung lesions, and 3 of these lung lesions were at least 3 cm.

Since this was a left-sided tumor and RAS wild-type, BRAF wild-type, the discussion really came to the choice of biologic of an EGFR inhibitor versus a VEGF inhibitor, so bevacizumab versus cetuximab or panitumumab plus chemotherapy was started with the patient. The patient did not wish to proceed with the EGFR inhibitor because of the concern of her rash. She just did not want to carry that rash.

So, the decision was to start with FOLFOX/bevacizumab. The patient did seem to have a good response to FOLFOX/bevacizumab, and within 4 months after the response was confirmed by a repeat CT scan, the patient was placed on maintenance capecitabine and bevacizumab.

The location of the tumor does impact somewhat what we do—in the United States, less so, frankly, than in Europe. In the United States and in my practice, when I think about the right-sided tumor, it’s clearly an easy decision. EGFR inhibitors do not seem to have much activity. In fact, there’s even a concern in some patients that there may be some slight detriment. So, on the right side, it’s a very simple decision to go with chemotherapy plus bevacizumab—so, FOLFOX or FOLFIRI.

On the left side, the story is a little bit more complicated. We have data from prior phase III CALGB 804045 and data from various studies that suggest that perhaps in this group of patients, EGFR inhibitors may have a slight edge when combined with chemotherapy versus VEGF inhibitors. But that slight edge certainly has to be balanced with the risks of toxicities. So, although the discussion is a little bit different in a RAS wild-type, BRAF wild-type, I’d say a HER2-nonamplified, microsatellite-stable patient who has a tumor on the left side, the discussion that should ensue is that there is the option of an EGFR inhibitor, although the preference remains for a VEGF inhibitor first, if possible, versus an EGFR inhibitor. But, I think we are obligated to have the discussion because of the data that suggested there may be that slight advantage with the EGFR inhibitors started first in this group of patients.

Cardiac comorbidities are certainly factors. However, atrial fibrillation is not a contraindication for the use of bevacizumab. Usually, the concern is if patients have an arterial thrombolic event—arterial clot rather than a venous clot—that is not treated or has not been stabilized with treatment. So, in this patient, there’s certainly perhaps a slight risk that may increase the risk of clotting because of the atrial fibrillation. But it’s a very small risk, and the patient is already on anticoagulation.

Now then, the next question is—of course, this patient is on anticoagulation—should we be concerned about an anti-VEGF agent? And the answer has been answered a long time ago in multiple studies: As long as the level of anticoagulation is well controlled within the parameters, there’s really no risk of added risk of bleeding for the patient. So, in my viewpoint for patients like that, I would not be worried about anti-VEGF or anti-EGFR therapy.

Transcript edited for clarity.

Metastatic Colorectal Cancer Originating on the Left Side

October 2016

• A 64-year-old woman underwent left hemicolectomy for an obstructing mass at the rectosigmoid junction
  • PMH: atrial fibrillation, moderately controlled on a beta- blocker; patient is also on warfarin
  • CEA elevated; 23.3 ng/mL
• Pathology:
  • Undifferentiated adenocarcinoma, invading through the muscularis mucosae up to the pericolic fat; 14 nodes were biopsied, 10 were involved
  • Molecular testing:RASandBRAFwild-type, microsatellite stable
• Imaging with PET/CT showed multiple lung lesions bilaterally, three measuring approximately 3.0 cm
• Diagnosis: grade 3 colorectal adenocarcinoma, stage T4N2M1
• The patient preferred to avoid rash and received systemic therapy with FOLFOX + bevacizumab; therapy was well-tolerated
• Follow-up imaging at 2 months and 4 months showed significant response in the lung lesions
• The patient was continued on bevacizumab maintenance

August 2017

• The patient complained of nausea and fatigue
• CT of the chest, abdomen, and pelvis showed marked progression in two of the lung lesions and development of 3 small liver lesions
• The patient was switched to FOLFIRI and cetuximab; her heart rhythm was closely monitored and remained stable
• Follow-up imaging at 2 months and 4 months showed stable disease in the lung and liver lesions; her symptoms improved
• At 4 months, the patient complained of severe fatigue and was changed to maintenance therapy

January 2018

• At 5 months, the patient reports reappearance of symptoms and states she requires frequent rest because of fatigue
• CEA, 89.8 ng/mL
• CT shows progressive disease in the lung and presence of several small boney lesions
• The patient is motivated to try another therapy