Stay tuned for our LIVE OncLive News Network coverage straight from the #ASH18 conference floor! 

Select Topic:
Browse by Series:

Emerging Therapy in Metastatic Colorectal Cancer

Insights From: Tanios Bekaii-Saab, MD, Mayo Clinic; Johanna C. Bendell, MD, Sarah Cannon Research Institute
Published: Tuesday, Oct 16, 2018



Transcript:

Tanios Bekaii-Saab, MD:
The 2 most interesting areas for drugs—actually, there are 3. Of the 2, most pressing are the HER2-amplified tumors. We’re seeing a lot of great signals, and there are a number of studies that are looking at the HER2-amplified tumors. Across the board, we’re seeing those studies inducing significant responses with dual HER2-targeted blockade. It’s usually an oral and an IV [intravenous] agent, such as trastuzumab plus lapatinib, which was the first study. It was a very interesting small study. The next one that’s reporting out is HERACLES-B, which is essentially trastuzumab plus pertuzumab. And then there is my pathway study with trastuzumab and pertuzumab. There is the tucatinib plus trastuzumab study that’s ongoing. All these studies hold their promises, and we hope to have a standard for our patients with HER2-amplified tumors soon. This is 4% of the patients, a reasonable chunk, that we need to pay attention to. So, that’s one.

The other option, or the other area, that I think is very exciting is immune therapy. We had a big, big, big disappointment with IMblaze370, which essentially looked at atezolizumab and cobimetinib, with the hopes that they would transform cold tumors to hot ones in the microsatellite-stable space. This was a negative trial. It really introduced a lot of notions to this. That disappointment slowed down progress in this particular arena, but it did not—and should not—stop the development of options for patients with microsatellite-stable colorectal cancer who may still be eligible for immune therapy options. Some of the more recent studies include agents that target pathways other than MAPK that essentially increase the level of tumor-infiltrating lymphocyte proliferation.

There’s also the microphage inhibitors, like CSF1R inhibitors, that are being combined with PD-1 inhibitors, essentially bringing those good microphages into the tumor and excluding the bad ones. It’s shifting the balance and increasing the level of antigen presentation and likelihood of PD-1 to be available. A number of other permutations in colorectal cancer could essentially, hopefully one day, help immune therapy to make its way into microsatellite-stable colorectal tumors in addition to the advances we’ve seen with MSI [microsatellite instability]–high disease.

Finally, there are the other targets, and there are a number of them that are being looked at and being developed. We have a specific platform going through our ACCRU [Academic and Community Cancer Research United] network, which is a Mayo Clinic-supported consortium of about 100 institution and private practices, community practices, that is essentially trying to look at breaking down colon cancer into a lot of different diseases and finding a target for each one of those disease subgroups in a study we call COLOMATE. We already have a number of studies that have been built in on top of the HER2 study in this platform, and we continue to build on that.

This is the future of where we want to go with this disease, and I think we’re just seeing the tip of the iceberg right now. The rest of the iceberg is going to become clearer and clearer with time, and I think ultimately, we’re going to be able to target every subgroup of colon cancer with the appropriate agent or combination of agents.

Johanna C. Bendell, MD: As we learn more about the molecular profiling of patients with metastatic colorectal cancer, we have found that certain targeted agents hold promise for treating patients. We think about things like HER2-positive disease potentially responding to HER2 inhibitors. We saw from the HERACLES study that the combination of trastuzumab plus lapatinib gave response rates in the 30% to 40% range for these patients with durable responses. And we saw in the My Pathway study that the combination of trastuzumab plus pertuzumab showed response rates in the 40% range with durable responses. That showed, for this particular population, these targeted agents hold a lot of promise.

Another agent that we’re very excited about that’s shown some initial promising data is something called CEA-TCB. This is a bispecific antibody that binds to CEA in the tumors and then binds to the T-cell receptor and brings the T-cells to the tumors directly. We’ve seen some preliminary data with both the single-agent bispecific antibody and this bispecific antibody in combination with atezolizumab, which have shown some responses in patients with refractory and microsatellite-stable colon cancer that are very durable. We’re waiting to see more of what happens as this molecule gets developed further.

Transcript Edited for Clarity.
Slider Left
Slider Right


Transcript:

Tanios Bekaii-Saab, MD:
The 2 most interesting areas for drugs—actually, there are 3. Of the 2, most pressing are the HER2-amplified tumors. We’re seeing a lot of great signals, and there are a number of studies that are looking at the HER2-amplified tumors. Across the board, we’re seeing those studies inducing significant responses with dual HER2-targeted blockade. It’s usually an oral and an IV [intravenous] agent, such as trastuzumab plus lapatinib, which was the first study. It was a very interesting small study. The next one that’s reporting out is HERACLES-B, which is essentially trastuzumab plus pertuzumab. And then there is my pathway study with trastuzumab and pertuzumab. There is the tucatinib plus trastuzumab study that’s ongoing. All these studies hold their promises, and we hope to have a standard for our patients with HER2-amplified tumors soon. This is 4% of the patients, a reasonable chunk, that we need to pay attention to. So, that’s one.

The other option, or the other area, that I think is very exciting is immune therapy. We had a big, big, big disappointment with IMblaze370, which essentially looked at atezolizumab and cobimetinib, with the hopes that they would transform cold tumors to hot ones in the microsatellite-stable space. This was a negative trial. It really introduced a lot of notions to this. That disappointment slowed down progress in this particular arena, but it did not—and should not—stop the development of options for patients with microsatellite-stable colorectal cancer who may still be eligible for immune therapy options. Some of the more recent studies include agents that target pathways other than MAPK that essentially increase the level of tumor-infiltrating lymphocyte proliferation.

There’s also the microphage inhibitors, like CSF1R inhibitors, that are being combined with PD-1 inhibitors, essentially bringing those good microphages into the tumor and excluding the bad ones. It’s shifting the balance and increasing the level of antigen presentation and likelihood of PD-1 to be available. A number of other permutations in colorectal cancer could essentially, hopefully one day, help immune therapy to make its way into microsatellite-stable colorectal tumors in addition to the advances we’ve seen with MSI [microsatellite instability]–high disease.

Finally, there are the other targets, and there are a number of them that are being looked at and being developed. We have a specific platform going through our ACCRU [Academic and Community Cancer Research United] network, which is a Mayo Clinic-supported consortium of about 100 institution and private practices, community practices, that is essentially trying to look at breaking down colon cancer into a lot of different diseases and finding a target for each one of those disease subgroups in a study we call COLOMATE. We already have a number of studies that have been built in on top of the HER2 study in this platform, and we continue to build on that.

This is the future of where we want to go with this disease, and I think we’re just seeing the tip of the iceberg right now. The rest of the iceberg is going to become clearer and clearer with time, and I think ultimately, we’re going to be able to target every subgroup of colon cancer with the appropriate agent or combination of agents.

Johanna C. Bendell, MD: As we learn more about the molecular profiling of patients with metastatic colorectal cancer, we have found that certain targeted agents hold promise for treating patients. We think about things like HER2-positive disease potentially responding to HER2 inhibitors. We saw from the HERACLES study that the combination of trastuzumab plus lapatinib gave response rates in the 30% to 40% range for these patients with durable responses. And we saw in the My Pathway study that the combination of trastuzumab plus pertuzumab showed response rates in the 40% range with durable responses. That showed, for this particular population, these targeted agents hold a lot of promise.

Another agent that we’re very excited about that’s shown some initial promising data is something called CEA-TCB. This is a bispecific antibody that binds to CEA in the tumors and then binds to the T-cell receptor and brings the T-cells to the tumors directly. We’ve seen some preliminary data with both the single-agent bispecific antibody and this bispecific antibody in combination with atezolizumab, which have shown some responses in patients with refractory and microsatellite-stable colon cancer that are very durable. We’re waiting to see more of what happens as this molecule gets developed further.

Transcript Edited for Clarity.
View Conference Coverage
Online CME Activities
TitleExpiration DateCME Credits
Community Practice Connections™: Oncology Best Practice™ Decision Points in Advanced NSCLC: Assessing Treatment Options Beyond Disease ProgressionNov 30, 20181.0
Community Practice Connections™: Precision Medicine for Community Oncologists: Assessing the Role of Tumor-Testing Technologies in Cancer CareNov 30, 20181.0
Publication Bottom Border
Border Publication
x