A Variety of Treatment Options Are Becoming Available in CRC

Kristen K. Ciombor, MD, MSCI

Assistant Professor

Division of Hematology/Oncology, Department of Medicine

Vanderbilt University Medical Center

Nashville, TN

Kristen K. Ciombor, MD, MSCI, recently spoke at an Around the Practice® discussion regarding treatment updates, molecular testing options, and emerging targets in the world of metastatic colorectal cancer (CRC). She discussed these updates with CancerNetwork® and highlighted ongoing research in the space, the importance of multidisciplinary care for patients with CRC, and the most important presentations from the 2023 European Society for Medical Oncology (ESMO) Congress.

At your institution, what are the current treatment sequencing options in CRC?

At Vanderbilt, we have a lot of clinical trials open. Those like the phase 3 BREAKWATER [NCT04607421] and the phase 3 MOUNTAINEER-03 [NCT05253651] trials are about to open at our institution.^1,2 We’re thinking early on in terms of targeted treatment options for patients with CRC. There are good standard-of-care options from the beginning that are targeted: for instance, immunotherapy for patients who have microsatellite instability [MSI]–high [disease]. Then we have a lot of chemotherapy options, even for patients who are not in clinical trials. The good thing is, in CRC, we’re adding more regimens because patients often need a variety of treatments over the years.

Can you speak to the importance of multidisciplinary care in the space?

Multidisciplinary care is essential in CRC. One of the most fun things about my job is interacting with my colleagues, who are colorectal surgeons, surgical oncologists, pathologists, radiation oncologists, interventional oncologists, and radiologists. All those people are behind the scenes. Sometimes they’re in front of the patients as well, but all of them are working together with me to ensure the care of the patient is optimal.

Looking forward, how do you hope to see the field evolve in the next 5 years?

I’m hoping that we see more treatment options for patients and we identify more patient subtypes that we can target and find actionable alterations for. I also hope that we find more treatments that are durable. We’re seeing that a little bit in immunotherapy and even with some of the trastuzumab [Herceptin]/tucatinib [Tukysa] data. However, I’d like to see more treatment options that are less toxic and more durable in terms of response.

What data presented at ESMO in the gastrointestinal space were you are most excited about?

At ESMO, we [presented] some more biomarker data on the phase 2 MOUNTAINEER study [NCT03043313].³ I’m also interested in looking at some updated data in the phase 3 KEYNOTE-811 trial [NCT03615326] in the esophageal space.⁴ I know it’ll be a great meeting, as they always are.

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

I think the biggest takeaway for me is that there are so many options in the HER2- amplified space in CRC, which is nice to see. It takes some thought. It is specific to CRC because how we treat HER2-positive breast cancer is not how we treat HER2-positive CRC. The nuances of the data are key. Knowing how to apply those in each individual patient is important.

Are you currently involved in any ongoing research?

I have an ongoing phase 2 ECOG study, ECOG-ACRIN [EA]2201 [NCT04751370], which is looking into the rectal cancer space for [patients]with MSI-high, locally advanced rectal cancer being treated with immunotherapy.⁵ [Patients are given] nivolumab [Opdivo] and ipilimumab [Yervoy] plus or minus 4 courses of radiation. We’re currently at the interim analysis, and we’re looking forward to seeing the results of that soon.

REFERENCES

1. Kopetz S, Grothey A, Yaeger R, et al. BREAKWATER: randomized phase 3 study of encorafenib (enco) + cetuximab (cetux) ± chemotherapy for first-line (1L) treatment (tx) of BRAF V600E-mutant (BRAFV600E) metastatic colorectal cancer (mCRC). J Clin Oncol. 2021;39(suppl 15):TPS3619. doi:10.1200/jco.2021.39.15_suppl.tps3619
2. Bekaii-Saab TS, Van Cutsem E, Tabernero J, et al. MOUNTAINEER-03: phase 3 study of tucatinib, trastuzumab, and mFOLFOX6 as first-line treatment in HER2+ metastatic colorectal cancer—trial in progress. J Clin Oncol. 2023;41(suppl 4):TPS261. doi:10.1200/jco.2023.41.4_suppl.tps261
3. Strickler JH, Cercek A, Siena S, et al; MOUNTAINEER Investigators. Tucatinib plus trastuzumab for chemotherapy-refractory, HER2-positive, RAS wild-type unresectable or metastatic colorectal cancer (MOUNTAINEER): a multicentre, open-label, phase 2 study. Lancet Oncol. 2023;24(5):496-508. doi:10.1016/S1470-2045(23)00150-X
4. Janjigian YY, Kawazoe A, Bai Y, et al. Pembrolizumab plus trastuzumab and chemotherapy for HER2+ metastatic gastric or gastroesophageal junction (mG/GEJ) adenocarcinoma: survival results from the phase III, randomized, double-blind, placebo-controlled KEYNOTE-811 study. Ann Oncol. 2023;34(suppl 2):S851-S852. doi:10.1016/j.annonc.2023.09.1424
5. Ciombor KK, Hong SC, Eng C, et al. EA2201: an ECOG-ACRIN phase II study of neoadjuvant nivolumab plus ipilimumab and short course radiation in MSI-H/dMMR rectal tumors. J Clin Oncol. 2022;40(suppl 16):TPS3644. doi:10.1200/jco.2022.40.16_suppl.tps3644