Clinical Approach for Left-Sided Metastatic Colorectal Cancer - Episode 1
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 primaryRAS 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 doin 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 eventarterial 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 isof 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