Expert Discusses Treating Patients With NRAS-Mutated Colorectal Cancer

Narrowing down patients withNRAS-mutated colorectal cancer may help formulate new patient-specific treatments, according to Maria Ignez Braghiroli, MD.

In an interview withTargeted Oncology, Braghiroli, medical oncologist, Instituto do Câncer do Estado de São Paulo, discusses a study that parsed out patients with solelyNRAS-mutated colorectal cancer, what the current treatment paradigm is for these patients, and how the mutation status of a patient with colorectal cancer may affect their treatment.

TARGETED ONCOLOGY:Can you tell us about clinical characteristics of patients with metastatic colorectal cancer harboringNRASmutations?

Braghiroli:

We've been trying to molecularly characterize the type of tumors, and possibly try to individualize treatment. What we did is we selected all the colorectal cancer patients that were found to haveNRASmutations from 2008 to 2015 that were treated at Memorial Sloan Kettering. We found a total of 87 patients, and we had to exclude 3 patients because they had concurrentKRASmutations and we wanted the patients withNRASmutations only. Then we compared this population in terms of clinical characteristics, molecular characteristics, and outcomes to treatment in the population withKRASmutations and allRASwild type tumors.

TARGETED ONCOLOGY:You excluded patients withKRASmutations. How would that have affected the results?

Braghiroli:

We don't really know, and that's why we excluded only 3 that had both theNRASandKRASmutations. That's why we didn't include them in theNRASmutated patients only.

TARGETED ONCOLOGY:What would you say the current treatment paradigm is forNRAS-mutant metastatic colorectal cancer?

Braghiroli:

Basically, we know that anti-EGFR medications don't work forKRAS-mutant patients and also theNRAS-mutant patients. These are the smaller proportion of patients with colorectal cancer, around 3% to 7%. That's why we don't really know what happens to this specific subtype ofRASmutation patients, and that is why we were looking into it.

TARGETED ONCOLOGY:How much would you say mutation status affects the individual treatment of patients with colorectal cancer?

Braghiroli:

Specifically for theRAS-mutated patients, we know that they do not respond to the anti-EGFR mutations. In general, we know that maybeBRAF-mutated patients have a much worse prognosis, and the studies currently focused onBRAFinhibitors or MEK inhibitors, or a combination ofBRAF, MEK, and anti-EGFR inhibitors in these patients. That is actually being performed at Memorial Sloan Kettering also. A small subtype of patients actually have an amplification of HER2, for example, and they might benefit from anti-HER2 treatment.

There is also a sub-population that has its microsatellite stability, and maybe this population benefits from immunotherapy. So we are tending to find a small, specific subtypes of tumors, and then individualize their treatment in this way.

TARGETED ONCOLOGY:Are there any ongoing or planned studies in this space that you are particularly excited about?

Braghiroli:

There are many studies in immunotherapy. I think this is very interesting, and so far for the sporadic type of colorectal cancer, we seem to not have very good results, so I think studies focusing on that will be very interesting.

TARGETED ONCOLOGY:What do you hope to see in the next 5 to 10 years in the treatment of colorectal cancer?

Braghiroli:

Immunotherapy is one thing. I think we might understand left or right sided, and if this is really important for patients and if that has any implication for treatment. Hopefully, we'll have newer medications with more consistent improvement in survival, and maybe earlier detection via colonoscopy. It's not an easy procedure to perform for the patients, and there have been ongoing studies on fecal identification of tumor cells. That, or maybe blood identification of tumor cells to try to find them earlier.

TARGETED ONCOLOGY:What role does sidedness play in colorectal cancer?

Braghiroli:

There has been some evidence that patients with right-sided tumors may have a worse prognosis than patients with left-sided tumors. In our population withNRAS-mutated patients, the patients did worse than allRASwild-type tumors, but interestingly, they had more left-sided tumors than right-sided tumors. This is still a matter of research.