Future CRC Treatment to Focus on Mutation Status, Expert Says

Tanios S. Bekaii-Saab, MD, recently moderated an Around the Practice discussion regarding treatment updates and real-world applications in metastatic colorectal cancer (CRC). After the program, he spoke with CancerNetwork about first-line treatment options, the importance of multidisciplinary care, and upcoming FDA approvals that may affect the space.

Tanios S. Bekaii-Saab, MD, gave an overview of colorectal cancer along with current standard of care, and potential treatment options.

What are the current treatment sequencing options at your institution?

The landscape in metastatic CRC has become quite complex, and sequencing patterns depend on genomic alterations, the age of the patients, and performance status. There are a lot of factors that enter the equation as we think about our first line of attack, then second line, third line, etc. What’s happening more and more is we’re finding a lot of these biologics and immunotherapeutics for those patients where that is an indication and where the target is present. We’re starting to move those to earlier lines of therapy, either [in] clinical trials or as part of our clinical practice, for those patients who [have] microsatellite instability [MSI]-high [disease], starting with pembrolizumab [Keytruda] and then chemotherapy or other options for about 50% of those patients. For the majority of patients, chemotherapy remains the first line, plus or minus a biologic. A lot of the biologics that have been with the targeted biologics and later lines of therapies are being studied in the first line across multiple trials.

How do you use multidisciplinary practice in your clinic?

When we think about multidisciplinary care, we always think about the earlier stages of the disease. In metastatic CRC, multidisciplinary care remains important across all stages of cancer. For metastatic disease, especially with oligometastatic disease—meaning disease limited to 1 organ [such as] the liver, lung, or peritoneal cavity—it is very important to continue to integrate other disciplines into the care of patients, such as interventional radiologists [and] surgeons, and [it’s important] even in some cases [of] colon cancer, metastatic to the liver only, where we’ve been considering transplant options for some patients. The multidisciplinary care for patients with metastatic CRC and perhaps more specifically [for] those with oligometastatic CRC is key for enhancing the care of patients.

How do you hope to see the field evolve in the next 5 years?

The world of treating patients with metastatic CRC in the next 5 years will look more like what lung cancer, for example, looks like today. We’re going to stratify patients with subgroups according to their genomic alterations or even immune biomarkers that would help us [create] targeted [therapies] specifically to a molecular or genetic alteration in the cancer. We won’t [focus on] 1 colon cancer or 2; we will be dealing with multiple subgroups of CRC as we move forward over the next 5 years.

Fruquintinib is currently pending approval for patients with metastatic CRC. If approved, how would the treatment landscape change?

Fruquintinib [Elunate] is an oral multikinase inhibitor. It’s an interesting agent that targets VEGF receptors more specifically than other tyrosine kinase inhibitors, and it tends to be a little cleaner, meaning it doesn’t have as many off-target [responses]. Fruquintinib was looked at in patients who had received multiple lines of therapy, about 40% of the population, and included either treatment with TAS-102 [trifluridine/tipiracil] or regorafenib [Stivarga]. If approved, [fruquintinib] will add value for those 80% of patients with metastatic CRC who do not have alterations that we can target, such as BRAF or HER2. About 80% of the patients with CRC will go through chemotherapy in 1 or 2 lines and then will find themselves in a place other than clinical trials because we don’t have approved targeted agents [in the space]. Fruquintinib will join regorafenib and TAS-102 plus bevacizumab [Avastin] in a more complicated landscape in second line or third line and beyond for patients with refractory metastatic CRC.

What is your biggest takeaway from the discussion with your colleagues today?

The biggest takeaway from the discussion with my esteemed colleagues today relates to further understanding the complexities that have emerged with the availability of multiple targeted options in metastatic CRC. Specifically, with the HER2 discussion, the importance of understanding what [the] immunohistochemistry [score of] 2+ [or] 3+ means in terms of sequencing patterns [and] the presence or absence of a RAS mutation and its implications on the utilization of trastuzumab [Herceptin], tucatinib [Tukysa], fam-trastuzumab deruxtecan-nxki [Enhertu], and others. With BRAF V600 mutations, it’s important to try to [target the] biology early. We also need to understand the complexities of this MSI-high BRAF V600E subgroup. Most importantly, with the discussion on the importance of clinical trials and participation in clinical trials [we see] that these agents that have significantly improved survival.