Goals of Therapy in Relapsed/Refractory CRC

Michael Morse, MD: There are a number of important goals in managing patients in later lines of therapy, and certainly we spend quite a bit of time talking with people about what those goals are. For many people, of course, survival is very important, yet it’s critical to maintain quality of life.

Some patients have significant symptoms from their cancer that also require palliation. So, during that discussion, we ascertain, for example, what types of symptoms the person is having from their cancer, what types of side effects that they had from their prior therapy, what type of diet they have, what type of energy level they have, and what are the activities that they want to achieve. We try to tailor the choice of therapy to those considerations.

During the conversation with this type of patient, we’re trying to understand their outlook and their prior side effects. And when I speak with them about the options, I tell them there are two options in this situation. We have trifluridine/tipiracil and we have regorafenib. They’re both oral agents. One is given over 2 weeks out of every 4-week course. One is given 3 out of 4 weeks. They’re given continuously as long as there appears to be benefit. We emphasize what some of the side effects would be. Trifluridine/tipiracil mainly causes neutropenia, whereas regorafenib can cause diarrhea and hand-foot syndrome. We also emphasize with people what their activity level is like. For example, this patient may be very active, may do a lot of work with their hands, and may want to avoid hand-foot syndrome. Other patients may be very sedentary; they’re not as concerned about that particular side effect. Some patients have problems with hypertension already and may not want to risk having higher hypertension or requiring more drugs. Again, that may steer us more towards trifluridine/tipiracil.

We consider prescribing trifluridine/tipiracil in patients such as the one in this example. She is maintaining a very good performance status. She wants to be active. She’s tolerated her previous therapy reasonably well. Although we’re not told that, we assume her blood counts have been adequate. She wants to avoid certain toxicities that would not allow her to continue being very active, so she may want to avoid hand-foot syndrome or diarrhea. She is also concerned about survival, of course, and we know that trifluridine/tipiracil increases survival as well. She also clearly fits the indication for it since she’s been through all the standard therapies so far, including the biologics.

Case Scenario 1:

• This is a 70-year old woman who 3 years ago presented with bloody stool.
• Medical history included type 2 diabetes; no other comorbidities.
• A colonoscopy revealed a 1.5 cm tumor in the sigmoid colon.
• A CT scan revealed multiple hepatic and pulmonary lesions.
• Biopsy of liver lesion and colon mass showed moderately differentiated adenocarcinoma, KRAS, NRAS, BRAF wild-type and MSS.
• Her ECOG performance status at the time was 0.
• FOLFIRI plus cetuximab was initiated.
• She later developed progressive disease.
• She was given FOLFOX plus bevacizumab.
• Her ECOG performance status is now 1.