Monitoring for Response and Side Effects in Advanced CRC

Michael Morse, MD:Unfortunately, we don’t really have a lot of predictors for benefit in advanced disease. First of all, for the two available agents, there are no biomarkers. There’s no test you can do that predicts who’s going to benefit and who isn’t. Furthermore, we know that people with a better performance status almost always do better with whatever therapy is used. But, what about the patient with declining performance status, at this point, after they’ve been heavily pretreated? It’s often difficult to predict how they’ll tolerate their therapy. That’s why I often will go with the drug that has the least side effects, just so we know we can get them through enough cycles to see whether there’s going to be real benefit from it.

When we have a patient who’s receiving trifluridine/tipiracil, we’ll see them about once a cycle, usually on day 1. We’ll review their labs, make sure they haven’t had any severe toxicity during the previous cycle. Of course, we hope they would have called us before then to tell us about those experiences, but we’ll review the dosing for the drug and make sure that they’ve taken it the correct way, that they didn’t miss any doses, or whether there was any issue that came up that prevented them from taking doses. We’ll make sure about whether we need to make a delay or a dose reduction at that point, and then proceed on to the next cycle and ask them to let us know if there’s any problems with that next cycle of therapy.

Now, we usually image people about every 2 to 3 cycles when they have refractory disease. We can get a CEA level along the way just to see if it’s dropping, and understand that there’s a very low RECIST criteria response rate with any therapy for advanced disease. So, we’re really focusing on progression-free survival improvements. We don’t expect to see major changes on the CT scans in terms of response, but I emphasize to patients, that’s okay, as long as the cancer isn’t growing, as long as their tumor markers are relatively stable. They’re probably getting benefit from the drug. And, as long as the side effects are manageable, then it’s something that they can stay on for a prolonged period of time to get the most benefit.

Managing fatigue in advanced cancer patients is very difficult and very complicated because there are many causes for it, and often all acting at the same time. We try to ascertain first, is it due to their therapy? We know that TAS-102 can cause mild fatigue, although fortunately, it’s not a major problem with it. It’s a little bit more of a common problem with regorafenib. However, patients may be fatigued from their advanced cancer, and maybe that’s worsened a little bit by being on chemotherapy. First, we try to determine: is the drug helping them? We look at the tumor marker. We may look at imaging. If it’s helping, then we really want to try to keep them on the drug. There are several options for dealing with that. One could lower the dose if it’s grade 3/4 and doesn’t seem to be improving. One could delay the dose if the fatigue is relatively mild and seems to get better in between the periods of time on drug and off drug. There are some pharmacologic interventions that are sometimes used. I think some of the simple activities like making sure people are getting out and doing some exercise, even if it’s a little walking every day, making sure that people are actually sleeping on a regular basis, and making sure they have things to occupy their time so they’re not feeling tired all the time, but have something to energize them are really important in addition to what we can do with the therapies.

Case Scenario 2:

• A 57-year old man presented for routine colonoscopy and was found to have a descending colon moderately differentiated adenocarcinoma. CEA pre-operatively was 6.
• Laparoscopic colectomy with colo-colonic anastomosis was performed. Final pathology showed a T3N2a (stage IIIb) lesion with 5/20 LNs positive. There was lymphovascular but no perineural invasion.
• Mutation testing revealed a KRAS mutation. The tumor was MSS.
• His ECOG performance status was 0.
• Following surgery, he was given adjuvant therapy with FOLFOX for 12 cycles with oxaliplatin help during the last two cycles because of grade 2 neuropathy.
• Six months later, follow-up imaging revealed recurrence and multiple metastatic hepatic lesions.
• The patient was started on FOLFIRI plus bevacizumab.