Personalized Approaches to Treatment of Metastatic Colorectal Cancer - Episode 6

Preferences for Second-Line Therapy for mCRC

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Drs Cathy Eng and Joleen M. Hubbard explain how patients with metastatic colon cancer typically respond to initial treatment and describe the factors that impact second-line treatment decisions.

Tanios S. Bekaii-Saab, MD: Along the lines of thinking about treatment of metastatic colorectal cancer as more like a marathon, rather than a sprint; we’re thinking about 2, 3, 4, plus lines of therapy. We’ve touched upon the shared decision-making points, across moving from one line to the next.

What do we know about responses in beyond first line, and is response actually the goal, or is it stable disease, or a little bit of response? What exactly are the factors that come to mind, when you’re choosing your second-line therapy, and beyond?

Joleen M. Hubbard, MD: For second-line therapy, in general, we’re usually not seeing very much of a response. It ranges from the various second-line trials that we have, anywhere from 5% to 15%, sometimes upward of 20%. But that’s really optimistic. Usually, we’re seeing a very minimal response.

The one time we really need a response is if patients are symptomatic of their disease. In that situation, if they’re RAS/BRAF wild type and they hadn’t used an EGFR inhibitor before, that might be a situation where I’d use an EGFR inhibitor to try to augment the response in the second line if they were really symptomatic.

For the most part, I’m continuing a VEGF inhibitor into the second line, mainly because response usually isn’t the goal. It is typically progression-free survival that we’re looking at, as well as trying to maintain some quality of life. I usually start FOLFOX [folinic acid, fluorouracil, oxaliplatin] or FOLFOXIRI [folinic acid, fluorouracil, oxaliplatin, irinotecan], in the first-line setting.

In the second-line setting, usually people still have some residual peripheral neuropathy, so instead of reintroducing oxaliplatin, I typically will move to an irinotecan-based regimen. I’m most commonly using FOLFIRI [folinic acid, fluorouracil, irinotecan ] for that since I don’t have good luck mixing capecitabine and irinotecan together.

It’s weighing the risks and the benefits. If they have a nice response but are getting fatigued from chemotherapy, you can make some adjustments. You can go back to maintenance fluoropyrimidine, BEV [bevacizumab]. You can go to a single agent, to irinotecan. There are a lot of things you can do to make adjustments to help ensure the quality of treatment because you’re right, it is a marathon. We’re just trying to balance that quality and that quantity as long as we can.

Tanios S. Bekaii-Saab, MD: Most physicians in the US prefer oxaliplatin, Dr Hubbard does. Dr Eng, you actually prefer for many patients to start with irinotecan if it’s not a triplet. Any differences? Why irinotecan first?

Cathy Eng, MD, FACP, FASCO: Irinotecan, overall, is tolerated extremely well, except for the alopecia, which is not pleasing to many patients. They don’t want the alopecia; often our male patients ask me about the alopecia as well. Overall, they don’t have to worry about the cold toxicity, they can eat or drink whatever they want. A lot of what I do is asking the patient what their hobbies are. If they’re a surgeon, which can be problematic, a musician, if they like going hunting and they’re out there with a big gun, I would like them to feel their extremities. That would be my preference. I usually do ask them, and then they ask me, what’s the difference? I tell them the response rate’s the same, but obviously, the toxicities are different. That’s how I make the decision.

Transcript Edited for Clarity