DR HECHT: The patient was a 70-year-old woman who had originally presented with Stage II colon cancer, KRAS wild type, and Stage II — people — but that’s a different discussion, but this patient received no adjuvant therapy. Actually, I don’t remember the MSI status. Then, about a year ago, she was found on follow-up to have increasing CEA and had inoperable disease, had both visceral disease with liver metastases as well as intra-abdominal lymphadenopathy.

Since she was at UCLA and being treated by me, she was started on CAPOX plus bevacizumab and had a nice response and was well tolerated. After 6 cycles, the oxaliplatin was dropped and she was —

DR LOVE: That was dropped. She wasn’t having any problems with neuropathy?

DR HECHT: She had some mild neuropathy, but that’s our standard, to drop the oxaliplatin. And then she was continued on — you can call it maintenance, capecitabine and bevacizumab and did well for a period of time.

She’s 70 years old and she’s a real 70 years old, but not a particularly ill 70-year-old patient, with an ECOG of 1, some persistent mild neuropathy, not severe.

DR LOVE: Okay. So 10 or 11 months into treatment, she’s still feeling well?

DR HECHT: Yes. So asymptomatic. I’m sorry. I did not say that. Other than the mild neuropathy.

DR LOVE: So she’s feeling well.

DR HECHT: This is a radiologic progression.

DR LOVE: And what exactly was seen?

DR HECHT: There was some worsening of the liver metastases. Remember, she has extrahepatic disease as well.

DR LOVE: And what about the extrahepatic disease?

DR HECHT: The lymph nodes, if I remember correctly, probably were also a little bit worse as well. There weren’t any lung metastases.

DR LOVE: So Johanna, kind of a classic situation. I’m really curious what you all do. There are a number of options to consider. We’ll find out what happened to this lady, but what would you be thinking both on and off study?

DR BENDELL: So on study, an irinotecan-based regimen to move now into with the progressive disease. I’m hesitant to restart oxaliplatin in people who have the neuropathy still. For patients who are not being treated on clinical trial, what I see the most from my docs, and I tend to do as well, is just move into the FOLFIRI/bevacizumab combination, though I think sometimes we just do that out of habit more than anything else. But now we have some data to suggest that for patients who did well on bevacizumab in the first-line setting that continuation of bevacizumab may give some benefit within the second-line setting.

DR LOVE: What about aflibercept?

DR BENDELL: So I have not tended to use aflibercept for the patients that have done well on bevacizumab-based therapy during the first line. For patients who have rapid progression on bevacizumab, who are KRAS mutated, that’s the setting where I’d consider, outside of a clinical trial, personally, adding in aflibercept. But there are people in my practice who do switch to aflibercept/FOLFIRI for a patient like Randy’s. And I don’t think that there’s anything wrong, whichever way you want to choose.

DR LOVE: What happened with this lady?

DR HECHT: Like many of these patients, it’s a lot less common to get a response, even though most people in first line either get a response or stable disease. So the patient that you had said earlier, who kind of — hypothetical —there was actually a relatively small minority. And they tend to do poorly no matter what we do.

But stable disease is more common on patients than having really a second response. And the patient had stable disease for 2 scans and then progressed.

DR LOVE: Philip, what’s your approach to this generic situation of a patient who’s had, for example, FOLFOX/bev, now has slow disease progression, asymptomatic, as this lady?

DR PHILIP: We would — in my practice, I would put her back on a combination chemotherapy. In this case, it would be FOLFIRI plus bevacizumab, again, going back to the good benefit she’s had so far with her treatment. That would be my approach.

DR LOVE: And how do you approach the second-line therapy in a patient who blows right through, understanding that it’s not common, but how do you approach that, if they don’t seem to respond to, for example, FOLFOX/bev?

DR PHILIP: In a patient who I will start the FOLFOX/bev and say after the first CAT scan, if the second CAT scan is not doing well, that situation, CEA going up, especially symptomatic, I change the whole treatment. I will change them to FOLFIRI plus aflibercept at that point in time. That would be my approach.

DR LOVE: Charlie, what’s your approach?

DR FUCHS: I don’t think it’s unreasonable in a setting where somebody has progressed initially to switch to aflibercept. The problem is: I don’t know that aflibercept is necessarily a better drug than bevacizumab. They essentially hit the same target. So I don’t think it’s unreasonable to do it, intuitively, because what you tried first wasn’t working. I’m just not sure it’s going to turn it around.

DR LOVE: Any sense about why it seems like there’s not very much pickup of using aflibercept in the second-line situation? You hear repeatedly from investigators and physicians in practice, they’re more inclined toward bevacizumab. You say, “Why?”

“There’s data for both, and I’m used to it.” Is that pretty much it?

DR FUCHS: I think that’s it. You ask why not use aflibercept? I guess the counter is, why use it? Right? If you’re getting the same results with bevacizumab and your patient’s already on the drug and demonstrating tolerance to it, why switch?

DR LOVE: So — and again, you won’t see this teased out in a practice guideline. People understand there is no right answer. That’s one of the most common responses to our work is they like it when people say they don’t know what to do because they feel that way all the time, and they figure you do. And you may — but they are also interested in what you do in the face of or lack of perfect knowledge.

Colorectal cancer

Gastric cancer

Pancreatic cancer

Hepatocellular carcinoma

Gastrointestinal neuroendocrine tumors

Gastrointestinal stromal tumors