A. David McCollum, MD
The first-line setting for patients with colorectal cancer (CRC) has a handful of options; however, there are additional regimens that could show promise if moved upfront, explains A. David McCollum, MD.
on Gastrointestinal Cancers, McCollum discussed the optimal management of CRC in the first-line setting and the ongoing research with checkpoint inhibitors designed to benefit larger groups of patients.
OncLive: Can you discuss current developments in the field of CRC?
: We had a big burst of activity in the early part of this millennia when many new agents were approved. There was a decade of research to sort through to decide what the optimal therapy is—either with chemotherapy or a biologic agent—for patients with CRC. During that time, we understood that there were some molecular features that we could use as a biomarker to help predict optimal regimens for a particular form of CRC.
In my lecture, I mainly discussed optimizing first-line therapy. Some of the important points are that chemotherapy doublets and a biologic agent are standard as a first-line therapy. There are many options and there is not necessarily one best option. It is becoming clearer that the sidedness of the primary tumor may help to predict which biologic agent we should use. The EGFR-targeted agents do not seem to provide as much benefit for patients who have a right-sided primary tumor. We see that those are used more commonly in patients with left-sided tumors.
How do you determine the sequencing of these agents once a patient progresses after first-line treatment?
We would discuss a biologic drug with a combination chemotherapy platform. FOLFOX or FOLFIRI are standard-of-care regimens at this point. We treat to a maximum response. The maintenance studies have varied with how long patients are on treatment; it has been from 3 months all the way up to 6 months. There are some modifications needed in the intensity of the chemotherapy to maintain that benefit for as long as we can.
The best maintenance therapy for a patient depends on what their frontline regimen is. Some would argue that it is fluoropyrimidine alone where as others would argue it is fluoropyrimidine and a biologic agent. Some patients who are treated with an EGFR-targeted agent in the frontline setting believe that it could be a continuation of the EGFR-targeted agents alone or until patients have progression.
There is also some debate about what constitutes enough progression that you then need to transition onto second-line therapy. A lot of things go into play there, not necessarily how patients are doing radiographically, but also how they do clinically, where the progression is, or if the patient is symptomatic or not. There are many different features that go into that decision.
What current regimens in the pipeline are exciting?
The most exciting thing for the whole field of CRC is how to integrate the checkpoint inhibitors. We know the patients who have MSI-H phenotype or a mismatch-repair deficient immunohistochemistry profile seem to be the patients who derive the most benefit from PD-1/PD-L1 inhibitors. There are subsets of patients who are outside of that subgroup who also have some benefit, but patients with MSI-H tumors clearly have the most benefit.
The question now is, “Do we try to use these agents upfront?” There is an ongoing trial at my institution looking at chemotherapy versus a PD-1 inhibitor. It is accruing slowly, as it is only a small subset of patients and there is already a lot of belief in the community that this group needs to receive a checkpoint inhibitor.
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