Case 2: Maintenance Therapy in mCRC

EXPERT PERSPECTIVE VIRTUAL TUMOR BOARD

Shubham Pant, MD:Coming back to maintenance therapy, Richard, the case that you discussed was on maintenance therapy but with the biologic. First there was OPTIMOX1 and OPTIMOX2, which looked at maintenance therapy. Mike, what are your thoughts on maintenance therapy? Do you use the biologic or not? What do you use as maintenance therapy in your patients?

Michael Morse, MD:Clearly, the chemotherapy component, as we’ve seen time and time again, is an important part of maintenance therapy if you’re going to use it. As you pointed out, the OPTIMOX trials tell us that there is utility to continuing a chemotherapy drug. Oxaliplatin is obviously impractical to give long term, so it’s natural that we’re going to stop at 6 or 8 doses.

As far as adding on the biologic, we have data with bevacizumab plus chemotherapy that consistently show that there’s a progression-free survival benefit. In 1 study, there was an overall survival benefit. This was small, but there was a benefit to adding bevacizumab to chemotherapy. The reverse is not so clear, in using just the biologic. I think we see the same thing here in the VALENTINO trial, which is really not so much a study of the benefit—yes or no—of maintenance anti-EGFR therapy. It’s really, again, the question of, is a chemotherapy component important here? I think it proves, once again, that it is.

In general, the biologic adds only a small amount of additional toxicity. My opinion is that a biologic with chemotherapy is a bit better, in terms of progression-free survival. I would continue to use the biologic if we’re going to continue the chemotherapy.

Shubham Pant, MD:Great point. What about you, Richard? A biologic with VEGF has its own side effects, but a biologic with anti-EGFR as maintenance has its own side effects, as you said. Patients can get rash and fatigue, and there can be other issues. How do you tackle this problem with patients?

Richard Kim, MD:I agree with Mike. The concept of maintenance therapy came about because of oxaliplatin. We cannot do oxaliplatin forever, so we need to put up some maintenance therapy. There is a lack of data on the use of bevacizumab alone. Bevacizumab alone should not be used when there are data suggesting that you could possibly use the combination, or the 5-FU [fluorouracil] plus bevacizumab. There is clear data, as you said, of some progression-free survival benefit and some overall survival benefit in that setting. There are data that demonstrate that you can probably use 5-FU plus bevacizumab in the setting as maintenance therapy.

However, EGFR maintenance therapy is a question. I just presented VALENTINO data, which really do not answer the question of maintenance therapy. Rather, they just explore whether 5-FU plus panitumumab is better than panitumumab alone in maintenance therapy. The trial, to me, was a negative study. However, that sort of contradicts the MACRO2 study, which was a trial using cetuximab as maintenance therapy. You may know that the trial looked at FOLFOX [folinic acid, fluorouracil, and oxaliplatin] with cetuximab. I don’t remember exactly how many cycles, but after a certain number of cycles they were randomized to the continuation of FOLFOX/cetuximab or cetuximab alone. It was a noninferiority study, and it met its endpoint. Cetuximab was noninferior to FOLFOX with cetuximab.

So we have conflicting data here. With panitumumab, you have to give 5-FU. You could probably give cetuximab alone. I think that’s the problem in using cetuximab as a first-line therapy. I don’t know what to do for maintenance therapy. So it’s still a controversial area. If you’re a purist, there are data that suggest that you could use cetuximab alone as maintenance therapy. However, if you use panitumumab in the first-line setting, from the VALENTINO study that I showed you, you’d probably have to use 5-FU plus panitumumab because that seems to be better than panitumumab alone.

Shubham Pant, MD:But the chemotherapy is probably important. I think most of us, in clinical practice, do continue with a chemotherapy backbone and think about continuing the biologic on top of that.

This has been a great discussion. I just want to highlight the take-home points. For asymptomatic patients, the current data demonstrate that there’s really not much benefit in doing upfront resection in these patients. Obviously, it’s based on the clinical outcome of the patient and what their clinical situation is. In regard to tumor sidedness, the treatment options for left-sided tumors is anti-EGFR therapy or bevacizumab. On the right side, it is suggested not to use anti-EGFR therapy. I think that is very clear. So the right side is more clear than the left side. They’re still trying to figure out the left side. However, if you have a left-sided tumor, you’re going to do much better than if you have a right-sided tumor.

What to do in the second line is still unclear. We don’t have enough data. You could continue with an anti-EGFR therapy in the second-line or, possibly, third-line setting in these patients.

Looking at maintenance therapy, probably through the OPTIMOX data, you should continue with a chemotherapy backbone. Potentially, you could add on and continue with the biologic. You could also use single-agent cetuximab or the combination of 5-FU/panitumumab. That’s a lot to digest, but I think this was a great discussion. Thank you.

Transcript edited for clarity.