Exploring Unmet Needs to Optimize Neoadjuvant Therapy in Resectable CRC

Although neoadjuvant therapy is a feasible approach for patients with resectable colorectal cancer (CRC), further research could help optimize treatment strategies and patient selection for this approach, according to Richard Kim, MD.

In a presentation at the 2024 ASCO Annual Meeting, Kim discussed the neoadjuvant approach for patients with CRC, highlighting the potential benefits and risks of preoperative therapy, and noting the importance of tumor staging and the role of immunotherapy in certain patients.

“There are many unmet needs that we need to figure out [for patients with resectable CRC],” Kim emphasized in an interview with OncLive®.

In the interview, Kim discussed standard treatment approaches for patients with resectable CRC based on both the National Comprehensive Cancer Network (NCCN) Guidelines and emerging data; highlighted unmet needs for this patient population; and detailed emerging treatments in unresectable hepatocellular carcinoma (HCC).

Kim serves as the service chief of Medical Gastrointestinal Oncology and a senior member in the Gastrointestinal Oncology Department at Moffitt Cancer Center, and a professor of oncology at the University of South Florida College of Medicine in Tampa.

OncLive: What is the current treatment approach for patients with resectable CRC?

Kim: The neoadjuvant approach to resectable CRC varies depending on the institution. I would say that the standard treatment of resectable CRC is still surgical resection. However, if you look at the NCCN Guidelines, they say to consider giving neoadjuvant therapy in patients whose [tumors] are T4b or who have bulky disease.

If patients have a mismatch repair–proficient [pMMR] tumor, the recommendation is to give chemotherapy in [the neoadjuvant] setting. However, the recommendation is to try immunotherapies instead of chemotherapy in those patients with T4b, resectable mismatch repair–deficient [dMMR] tumors.

What are the unmet needs for patients with resectable CRC being treated in the neoadjuvant setting?

In pMMR [disease], we are trying to figure out which patients [truly] need neoadjuvant therapy. Based on the current technology we have, the staging is very inaccurate; the data will tell you that in anywhere from 15% to 25% [of patients], we are overstaging by our current criteria. We need to do a better job [with] staging, making this an unmet need. Second, if you do give neoadjuvant therapy, how many cycles do you give, and what do you do afterward? Those are the main areas [of need], at least in pMMR tumors.

In dMMR CRC, [neoadjuvant] immunotherapy does work; the data show that the past complete response rates are high. Similarly, if you do give immunotherapy, how many cycles do you give? How many cycles do you give after [surgery]? Well, a provocative question is if you can [preserve] the organ preservation, similar to rectal cancer. Can you [give a patient] immunotherapy and not do surgery? Those are still all unmet areas [of need].

What studies have the potential to shift the standard of care in the treatment of unresectable HCC?

From my perspective, the phase 3 CheckMate 9DW trial [NCT04039607] for [previously untreated] unresectable hepatocellular carcinoma [HCC] is one that could be practice-changing. It used the combination of nivolumab [Opdivo] and ipilimumab [Yervoy] in the first-line setting vs [investigator’s choice of] TKI [sorafenib (Nexavar) or lenvatinib (Lenvima)]. Those data [were] presented as a late-breaking abstract [at the 2024 ASCO Annual Meeting].

These data are very important because in the first-line setting of [unresectable] HCC, it's very crowded right now. We have data with atezolizumab [Tecentriq] plus bevacizumab [Avastin] based on the phase 3 IMbrave150 trial [NCT03434379], and there are data from the phase 3 HIMALAYA trial [NCT03298451] with the combination of durvalumab [Imfinzi] and tremelimumab [Imjudo]. These 2 regimens are currently FDA approved.

We heard most recently from the phase 3 CARES-310 trial [NCT03764293] that you can give a TKI and IO in this setting, showing overall survival benefits. Although this is not currently [FDA] approved, hopefully in the future, it will get approved.

[Based on outcomes of CheckMate 9DW], there may be another combination that can get approved in the first-line setting, giving us more options. As a clinician, we have to decide which regimen to choose from, although this depends on the efficacy and safety data.

Reference

Kim R. Neoadjuvant approach to localized colon cancer: ready for prime time? Presented at: 2024 ASCO Annual Meeting; May 31-June 4, 2024; Chicago, Illinois.