Therapeutic Approach at mCRC Progression

Tanios Bekaii-Saab, MD:Ten months following initiation of the treatment, the patient comes to the clinic feeling nauseous and fatigued, the symptoms suggestive of progressive disease. Scans get checked. The patient has progressive disease. So, the discussion ensues, and the decision is to shift her to second-line therapy. Although, part of the discussion also included perhaps reconsidering oxaliplatin, but because of some residual neuropathy, we decided to proceed with FOLFIRI plus cetuximab. Since this was a left-sided tumor, we didn’t want to wait too long for the line of therapies before starting the EGFR inhibitor.

The patient went on FOLFIRI/cetuximab, had some stable disease, and then at 4 months started showing evidence of symptoms that suggested progression again, which were confirmed by the scans. The patient failed on FOLFOX/bevacizumab going through the first-line setting, and then went on capecitabine/bevacizumab as a maintenance strategy. The discussion about what to do next includes 2 options: (1) switch complete therapy; (2) reinitiate oxaliplatin. Reinitiation of oxaliplatin is based on what we know from the OPTIMOX study and a little bit from the CAIRO study. We can get a small percent of patients to respond, 20%.

So, it’s not a major benefit, but it’s also important not to waste an additional line of therapy. This is usually limited by neuropathy for many patients. And the natural choice would be to proceed with FOLFIRI. We have 2 options: continuing with bevacizumab—so bevacizumab beyond progression—or switching the biologic to cetuximab or panitumumab. And given that the patient has a left-sided tumor, which is RAS wild-type, and we know that EGFR inhibitors do benefit those patients in earlier lines of therapy—perhaps with a much greater effect than, say, bevacizumab—and especially in the second-line setting where bevacizumab does not seem to add as much activity, the decision is taken to proceed with an EGFR inhibitor with cetuximab at that stage. Thus, the choice of FOLFIRI/cetuximab.

Four months following treatment with FOLFIRI plus cetuximab, the patient experienced significant fatigue. So, the question is, what do we do at this point of time? The difficulty with chemotherapy plus an EGFR inhibitor is that we do not have much data on maintenance strategies, unlike with chemotherapy plus bevacizumab followed by capecitabine plus bevacizumab. So, in this case, the chemotherapy is the primary contributor for the fatigue, we think. The decision was to drop FOLFIRI and to continue with single-agent cetuximab as a maintenance strategy, understanding that cetuximab is both relatively cytotoxic and cytostatic, and so it can serve as its own maintenance strategy.

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