The Biology of Extending Survival in Advanced CRC - Episode 6

Maintenance and Second-Line Decisions in mCRC


Tanios Bekaii-Saab, MD: From a practical standpoint, the data with maintenance EGFR therapy are lacking to the level that we have with VEGF inhibitors. I don’t disagree.

Dirk Arnold, MD, PhD: It’s not even necessary to do anti-EGFR therapy.

Tanios Bekaii-Saab, MD: Well, we don’t know that. Yes, we do.

John L. Marshall, MD: What do you do in that situation? If you start with EGFR—this is something I don’t do very often—and you reach 8 months, do you switch to a bevacizumab/capecitabine maintenance therapy? Do you maintain the EGFR single agent? What’s the practice strategy for those who are doing this in the frontline setting? How do you handle it?

Dirk Arnold, MD, PhD: Do oncology as we do oncology. Keep treatment as long as we do have a benefit or as long as the patient has the will to follow it.

John L. Marshall, MD: You keep it going as long as they can tolerate it?

Dirk Arnold, MD, PhD: The median treatment duration, in these trials, was not more than 6 months. I don’t say to stop every patient after 6 months, but you should consider the patient’s interest.

John L. Marshall, MD: Any maintenance therapy? Or stop them cold and wait?

Dirk Arnold, MD, PhD: No maintenance.

John L. Marshall, MD: No maintenance.

Fortunato Ciardiello, MD, PhD: In real life, in Europe, even with bevacizumab, even in mutant patients where you don’t have an alternative, maintenance therapy is not very often done. In most cases, between 6, 7, or 8 months in, you stop everything. You have reached the maximum efficacy that you can reach with first-line therapy.

We are working in a system where there is a 99%, or 100%, public health system. The interest is in the opposite side because, basically, you have space for more patients if someone stops therapy. In medium-sized or community hospitals, this is a key issue. Preferentially, I do bevacizumab treatment as long as necessarily possible. But I am a minority in my country. In terms of anti-EGFR maintenance therapy, there actually are some data.

John L. Marshall, MD: Yes, there are.

Fortunato Ciardiello, MD, PhD: It’s very simple. There is the data from the MACBETH randomized phase II trial in which modified FOLFOXIRI (folinic acid, 5-fluorouracil, oxaliplatin, and irinotecan) was added to cetuximab and then as maintenance therapy after 4 months of chemotherapy. Chemotherapy was stopped and either bevacizumab or cetuximab was given to the responding patients—and this is from the GONO study by Alfredo Falcone. There is a trend in favor of cetuximab or bevacizumab.

If it’s through the biology of emerging clones with RAS mutations, they disappear as long as you don’t treat the patient with anti-EGFR because there is no biology pressure any longer. One of the reasons why—in third-line, fourth-line, or fifth-line settings—anti-EGFR therapies could work in patients who responded in every line could be that now you have, again, clones that are RAS, BRAF wild-type—responsive. And then the study between bevacizumab/anti-EGFR in first-line therapy is a classic study between Americans and Europeans.

Tanios Bekaii-Saab, MD: A couple quick points. There is not enough evidence for EGFR maintenance therapy, as you have with bevacizumab. I totally agree, the difference—and that’s why I started the first point—is it’s practical and pragmatic. Our practices are very different and they rely on different ways to actually treat patients, how we view maintenance therapy and how we view long-term treatment versus our European colleagues. The nuances on the left are not as significant as the nuances on the right. And therefore, when you take this whole package, in terms of how I treat my patients in clinic for 2, 3, or 4 months, I take the route that makes it the easiest to treat my patient for the longest period of time. And that’s the nature of our practice, which is different than our European colleagues.

John L. Marshall, MD: So, we could agree to be different on that?

Tanios Bekaii-Saab, MD: But we don’t disagree on the principle.

John L. Marshall, MD: No. The lesson, I think, really is that we are increasingly enriching the patient who benefits from EGFR therapy. Distinguishing between right-sided colon cancer versus left-sided colon cancer clearly helps us do that. I think it’s a perfectly appropriate discussion that the patient should be engaged in—about risk and what our curves look like and toxicity and public versus the other counter argument of simplicity and the “We’re in this for the long haul” kind-of strategy. I think this is really important because we’re now taking, off the table, some patients who were getting EGFR therapy, and we’re enriching this group. The second point is that, then, biologics have a clear role. So, that’s part of our job—to find the right patient.

Transcript Edited for Clarity