Transcript:
Tanios Bekaii-Saab: Name is Tanios Bekaii-Saab. I'm a Professor of Oncology at Mayo Clinic, on the Arizona campus.
When we look at metastatic colorectal cancer, unlike with the earlier stages, we have a small percent of patients with MSI-high, microsatellite instability high. It's about 16 to 18 percent in the earlier stages.
That makes sense. In the earlier stages it seems to be protective of metastatic disease. In the later stages, to overwhelm essentially the immune system, these cancers are typically aggressive. They do confer a worse progressive.
MSI-high colorectal cancer was the worst prognostic element. It does respond to chemotherapy to a certain degree. But then with the advent of PD-1 inhibitor, what we've found is that for those patients with MSI-high metastatic colorectal cancer, you start seeing some meaningful and significant and durable responses.
In fact, with pembrolizumab as a single agent, the complete response in the initial study was 11 percent. That got up actually to close to 20 percent with the follow up, and that's just in the colorectal cancer patients who are deficient for MRR versus those that are proficient for MRR, with a zero percent response rate.
Now this was in a refractory patient population. The question that always comes about is, can we move these immunotherapy options to first line in the absence of data at this point in time?
We have some data from a study that was presented recently at ESMO with nivolumab and ipilimumab, which they show very solid results, including a survival and a progression free survival that was not reached.
We see a lot of patients who actually end up having the equivalent cure with single agent pembrolizumab, as I said maybe about 20 percent of them, maybe more. In fact, on that one study only four percent of the patients progressed with MSI-high colorectal cancer.
We do essentially have these responses continue beyond two years. When we stop pembrolizumab or now nivolumab plus/minus ipilimumab, we see those responses continue. You see those benefits to continue beyond stopping the immune therapies.
These tend to be quite tolerable. A very small percent of patients will have toxicities, but for the majority, especially with single agent PD-1, the toxicity is minimal. Whereby with the chemotherapy, we see a lot of toxicities. We can't sustain responses. There is no frank advantage for MSI-high to receive chemotherapy.
There is also absence of durable and complete responses with MSI-high patients. In fact, a lot of these patients, even if they have a good response progress very quickly, it would be difficult to salvage them.
Multiple examples exist on these patients with MSI-high that got pretreated and failed chemotherapy, and went to PD-1 inhibitors, and ended up with near lazarus effect. These patients went from performance status 3, ascites, almost bound to bed. Some of them were ever almost referred to hospice.
They come back, and most of them actually survive two, three, four plus years, and they continue to be survivors.
In my view point, one can make a very strong case for MSI-high colorectal cancer patients to receive the PD-1 inhibitor plus/minus the CTLA-4 inhibitor in the first line, rather than waste their time on chemotherapy.
Because again the response we see with immunotherapy cannot be matched by anything else we have today.
