The Treatment Goals of mCRC

Wells Messersmith, MD:The patient reported worsening weight loss, fatigue, and just general failure to thrive. And, again, a CT scan was done, which showed progression of disease. In this case, the patient had new liver nodules and lung nodules. We’re clearly in a palliative setting. So, the question becomes what therapy was given, and, in this case, irinotecan and cetuximab was chosen and the patient seemed to have some benefit with that, with some stable disease on the first re-staging scan.

The patient was switched to irinotecan and cetuximab, and then a PET/CT was obtained 3 months later, which showed stable disease. And overall, the patient seemed to get some symptomatic benefit for about 3 to 6 months after starting therapy.

The patient in this case did somewhat better than many patients do, so the time to progression (or progression-free survival) in the second-line setting is shorter than the first-line setting, and that makes sense. If a cancer is getting resistant to one type of chemotherapy—for instance, drug efflux pumps—or they’re turning off apoptosis pathways, it stands to reason they’re going to be more resistant to whatever you choose second-line. The benefit in the second-line setting is often less than the first-line, and that’s often true across multiple cancer types.

So, fairly typical story here: patient got second-line therapy, did okay for a while, and now is progressing, so you’re thinking about what are the options in the third-line setting. In fact, you have multiple options to choose from—in this case, a combination between a cytotoxic, irinotecan, and an EGFR inhibitor, a monoclonal antibody, with cetuximab. You could have also chosen panitumumab. One could argue, “Well, having a cytotoxic in the third-line setting, that might be a little much with the irinotecan,” and also the patient got worse on FOLFIRI, which has irinotecan in the first-line setting. But there is something about those 2 drugs. They seem to synergize pretty well, irinotecan/cetuximab. So, if the patient has a good performance status and you think they can tolerate it, it’s a very reasonable option.

You’ll note that in this case, a PET/CT was obtained after chemotherapy to look for response. And I just want to make a note that, in general, getting PETs/CTs to look for chemotherapy response is not in most of the guidelines. There’s definitely a role for PET/CT. We use it any time we’re going to surgery to make sure there’s not an occult disease somewhere. We use it when we’re going to do radiotherapy, for instance, because we want to make sure that there’s nothing hiding. We often use it for initial staging, but once someone is on chemotherapy, getting PET scan after PET scan is not only much more expensive, you’re also exposing them to a lot more radiation. And so, most of the guidelines will tell you that you really shouldn’t be using that to determine the response to chemotherapy. You should be sticking to CT scans and use PET scans for those other things that I mentioned.

Transcript edited for clarity.

September 2015

• A 71-year-old Caucasian male presented with severe left lower quadrant pain
  • He sought medical treatment after experiencing bloody diarrhea
• PMH: hypertension, managed with benazepril
• He is active and can perform daily activities without restrictions
• Laboratory findings: remarkable for CEA, 6.0 ng/mL
• Colonoscopy showed a mass in the descending colon which was biopsied
  • Pathological findings: Moderately differentiated adenocarcinoma
• NGS mutation testing results wereNRAS, KRAS, HRAS, HER2,andBRAFwild-type
  • Microsatellite stable
• CT of the chest, abdominal, and pelvis showed an 8-cm mass in the sigmoid colon
  • a 2-cm mass in the right lobe of the liver, and a 5-cm in the left lobe adjacent to the left hepatic vein
  • Impression: metastatic disease, borderline resectable
• Treatment was initiated with FOLFIRI + bevacizumab
• Imaging at 3 and 6 months showed decreased size of the liver nodules, but was not resectable

July 2016

• The patient complained of increased fatigue, requiring the need for frequent rest
• CT scan showed increasing size of the liver nodule (3 cm) and appearance of 3 new small liver lesions (<2 cm)
• He began therapy with FOLFOX + bevacizumab

February 2017

• The patient reported weight loss, increasing fatigue, and shortness of breath
• CT scan revealed progressive disease with no improvement in the primary and metastatic lesion size and/or number
• A new pulmonary nodule was seen in the right lung
• He was switched to irinotecan + cetuximab
• PET/CT at 3 months showed stable disease
• At 6 months, he reported moderate improvement in fatigue