Adjuvant Treatment or "Watch and Wait" in Stage II CRC



John Marshall, MD: Cathy, I have the hardest question of the morning for you. How do you decide in this stage II patient, who you’re going to watch and wait, and who you think should be treated, when you go in the room saying, “I think I’m going to recommend treatment for this patient?”

Cathy Eng, MD: I think it goes back to what Dustin mentioned earlier. For the high-risk stage II patients, we do have to take that into account, as well as the number of lymph nodes removed and the surgical technique. Multiple factors need to be taken into account, and that’s how all of us, individually, make the decision, as well as the discussion with the patient.

John Marshall, MD: Yes. We talked about stage II being a little different than stage III, probably biologically. Dustin, another hard question: Is rectal yet another kind of cancer? Should we apply the lessons learned in colon cancer to rectal cancer? What are your thoughts about that?

Dustin Deming, MD: I think we should think about the data that we’re collecting in colon cancer as applying to rectal cancer, but we also have to be very careful with how we apply that to rectal cancer. A big reason for that is the inadequacy of the clinical staging for rectal cancer. Unfortunately, even when we think we have a stage II rectal cancer, as many as 20% of those patients end up actually being stage III.

John Marshall, MD: The practice there is changing so quickly as well. It’s hard to know how to apply it. It’s a really good point. Tony, we spent a bunch of abstracts this year on the duration of adjuvant therapy. Do us a quick summary on 3 versus 6 months and your opinion, because I think this gives an opportunity for opinion on how to apply this data.

Tanios Bekaii-Saab, MD: The data that were presented at ASCO [American Society of Clinical Oncology annual meeting] come in 2 flavors. The first flavor is one study that…just confirms the findings from the IDEA trial, which is good. The second one was actually more interesting.

John Marshall, MD: Remind everybody what IDEA showed.

Tanios Bekaii-Saab, MD: IDEA essentially was a study that looked at 3 versus 6 months of oxaliplatin-based plus fluoropyrimidine, so CAPOX [capecitabine/oxaliplatin] or FOLFOX [folinic acid/fluorouracil/oxaliplatin], in patients with stage III colon cancer primarily, but there was a cohort of stage IIs as well. It was a noninferiority study. In the large patient population, the study did not meet its primary endpoint of noninferiority. As a statistical endpoint, it did not meet it, but clinically, I think it actually challenges us to reconsider how we treat patients in the adjuvant setting. In fact, we know one of the biggest challenges in the adjuvant setting is patients living the rest of their lives miserably with neuropathy because they were overexposed to oxaliplatin, which may have been unnecessary for most patients.

The study does confirm what the IDEA trial, the pooled analysis of close to 12,000 patients, suggested, which is that perhaps if you use capecitabine/oxaliplatin, even in the higher-risk patients, you may still get away with 3 months of capecitabine and oxaliplatin. With folinic acid/fluorouracil/oxaliplatin, that’s not true. With folinic acid/fluorouracil/oxaliplatin, you have to expose patients as much as tolerated for 12 months. These are your T4 and 1-plus. For patients with lower risk, you actually can get away with 3 months of capecitabine/oxaliplatin, and it definitely seems noninferior, but again, you’re breaking down subgroup analysis, which was secondary.

Now, the studies that were presented at ASCO—the Hellenic Society of Gastroenterology study, which was one of the larger ones, as well, on stage II and stage III colon cancers—did confirm 2 things. It confirmed the findings from IDEA, for example, that capecitabine/oxaliplatin may be okay for 3 months and folinic acid/fluorouracil/oxaliplatin is definitely for 6 months. For stage II, interestingly again, in that 1 study, same findings, the high-risk stage II look pretty much like the high-risk stage III in terms of risk stratification. Then, when they’ve done a prospective pooled analysis of all the stage II patients that were included in 4 trials—mind you that the study that came from the United States was a pure stage III study, the 80702—they found very similar findings to what they found with the stage III. For example, the principles that apply to stage III in terms of how we take decisions on 3 versus 6 will apply the same to your high-risk stage II patients.

What do I do? At this point of time, I’m still a minimalist in that standpoint. I like the 3 months for my patients. Whenever I have a discussion with the patients, and I understand I have my bias introduced, I try to have the discussion. With the low-risk patients, 3 months of capecitabine/oxaliplatin.

John Marshall, MD: You feel comfortable.

Tanios Bekaii-Saab, MD: I’m super comfortable. With the high-risk patients, including the high-risk stage II, the discussion I have is 3 months of capecitabine/oxaliplatin. I’ll have a discussion with you at 3 months about whether we want to continue with capecitabine. I actually do not believe that exposing patients to more than 3 months of oxaliplatin will add much benefit.

John Marshall, MD: Cathy, I know you feel very strongly about this, too. I look at this and say, “Well, OK, it wasn’t noninferior, but we know by how much it was inferior.” It’s a huge collection of patients, and even if there’s a delta, we now can measure that delta and, just like in our stage II patients, share that data and decide. As Tony says, neuropathy can be bad, but as you point out, they are living with neuropathy instead of dead, right? This is a big deal. Oncologists feel, I think, very vulnerable in this space, because if anybody relapses after adjuvant therapy, we all personally reflect and say, “What if I had? What if I had given more? Would they have been the 1% or 2% difference?” Give me your take on this data.

Cathy Eng, MD: Tony has given a very nice summary of what was discussed. I just want to make sure people do take into account that the Hellenic data were not a randomized study. It was based upon the physician's discretion of whether they would receive capecitabine/oxaliplatin or folinic acid/fluorouracil/oxaliplatin.

John Marshall, MD: For the 3 versus 6, it was which fluoropyrimidine, right?

Cathy Eng, MD: Right. Then for the pooled analysis of the 4 trials, a large part of the patients had received capecitabine/oxaliplatin versus the folinic acid/fluorouracil/oxaliplatin regimen, so the data are very interesting. Once again, though, it doesn’t take into account what we really do in real life, which is basically, give patients 3, maybe 4 months of oxaliplatin, and then we just continue, whether it be 5-FU [fluorouracil] or their Xeloda.

Transcript Edited for Clarity

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