Cathy Eng, MD, speaks to the unmet needs of treatment options in the management of metastatic colorectal cancer.
As the continuum of care for colorectal cancer has evolved, how would you assess the current treatment landscape as it relates to extending survival?
ENG: Regarding the continuum of care for colorectal cancer [CRC] in our current landscape of drugs available, I would say that we are doing our best to prolong the survival of our patients. We continue to have several drugs available to us, more recently oral agents. But more importantly, there is significance to making sure that patients get tested up front for molecular alterations, an analysis overall, to ensure that there is a possibility that they may or may not have a targetable agent that we can utilize. It could be more specific to the tumor and hopefully provide them greater benefit overall.
Can you discuss the importance of mutation status in treatment selection as well as any challenges or imminent needs when it comes to ascertaining individual mutation profiles?
ENG: I highly recommend that all physicians test their patients upfront with the largest panel available to them at their institution. You want to try to obtain as much information as soon as possible before the tumor specimen ends up in another warehouse or somewhere far away where it will take several weeks to obtain if you [need] that analysis. You really want to provide treatment options and to create some type of strategic planning for each patient once you are aware of their molecular analysis. It’s critical to optimize the care of our patients.
Some of the unmet needs that remain that are still not necessarily targetable are obviously patients that have RAS mutations. There was a lot of promise originally in AMG 510, specifically for a particular subtype of the KRAS mutation but the final updated results were not as groundbreaking as we had hoped for. Overall, our RAS-mutant population that is unable to receive anti-EGFR [epidermal growth factor receptor] therapy, specifically in the treatment-naïve setting with the right sided tumor, is still an area of unmet need. We need to find another treatment option for patients as well as options for patients that fail targeted therapy. Once immunotherapy patients or those with tumors that are MSI [microsatellite instability]-high progress, some do not respond as we had hoped, so we need to find other treatment options for those patients as well.
What else shapes frontline treatment selection and what can you share regarding patient factors?
ENG: For frontline treatment selection, it’s extremely important that decisions are based upon the other comorbidities of the patient, and I think that is one of the biggest factors in my decision making regarding sequencing. And I’m sure it’s the same for those in other positions as well. We have to take into account the psychosocial support that the patient has, as well as what options they have when it comes to getting to their provider for optimal management. Simple things such as transportation can be critical in the decision-making process.
What role do agents such as regorafenib and TAS-102 play in the metastatic CRC (mCRC) spectrum and to what extent can these extend survival?
ENG: The role of agents such as regorafenib and TAS-102 in the treatment of our patients with mCRC is still quite important. I know a lot of individuals don’t necessarily favor these drugs just because the role in the improvement of survival was not dramatically different in months from the control arm. But it is important to keep in mind that for patients with surgically unresectable disease, we have to provide a continuum of care to prolong their survival as much as possible, as long as their performance status is adequate and as long as their laboratory tests are within normal limits. We want to provide all potential options, and the advantages of regorafenib and TAS-102 are that they are oral agents and both drugs are being studied in clinical trials in combination with other drugs, so I think this is just the beginning. They are only FDA approved as single agents at this time, but I think they do have their advantages. They allow the patient to have the opportunity to be at home more with their family and to sometimes have a better quality of life. But these patients must be watched closely. Even though these are oral agents, I do like to see my patients every 2 weeks for the first 1 to 2 months, with bloodwork as well, just to make sure that they are tolerating the drug well, because you do not want to miss a potential adverse reaction or adverse event attributed to the drug such as diarrhea or nausea. Symptoms that can easily be treated as an outpatient as long as the patient is well instructed.
When it comes to using therapies, can you reflect on the factors that impact sequencing strategies or provide any tips about how to integrate these agents into the continuum of care?
ENG: Regarding the utilization of the newer agents, again regorafenib and TAS-102 are both oral agents and they are both FDA approved in refractory settings for metastatic disease. However, my personal tendency in a patient with significant tumor burden within the liver, where you may be a bit concerned about rising liver function tests, is to be a bit more cautious in using regorafenib, and follow the patient closely. Regarding patients who are receiving TAS-102, which has a tendency for significant myelosuppression, they must be followed closely for some potential toxicities that they may endure.
In regard to other, newer biologic agents, I cannot emphasize that I hope everybody is being tested for MSI from the very beginning of their diagnosis of colon cancer, regardless of stage. And any cancer patient should be tested for the NTRK fusion gene because it has many significances in other malignancies, not just CRC. So that would have a significant impact, especially in the setting of a cancer that has no standard of care. It would just be considered extremely rare.
How do you see the current gaps in treatment being addressed in ongoing and future research?
ENG: Overall, we need to identify new targets, new mechanisms of resistance, and even for patients that are responding to certain therapies such as anti-EGFR therapy, there are also documented mechanisms of resistance, and we need to learn how to overcome that as well. I know that’s a big feat, but because our surgically unresectable patients must remain on chemotherapy indefinitely, we really need to advance cancer research.