Joleen Hubbard, MD, Highlights The “Exciting Space” Of Metastatic CRC

In a recent discussion with CancerNetwork^®, Joleen Hubbard, MD, research collaborator withMayo Clinic and deputy director for clinical research at Allina Health Cancer Institute in Minneapolis, Minnesota, discussed new opportunities for patients with colorectal cancer (CRC).

In the discussion, Hubbard highlighted the potential of trastuzumab deruxtecan-nxki (Enhertu; T-DXd) in patients with HER2-expressing metastatic CRC based on studies including the phase 2 DESTINY-CRC01 trial (NCT03384940), which assessed the efficacy and safety of the agent in those who progressed after 2 or more prior regimens.¹ These trials may play a role in continuing HER2 inhibition downstream after the FDA approval of trastuzumab (Herceptin) plus tucatinib (Tukysa) in patients with metastatic HER2-positive CRC.²

Hubbard also discussed the phase 3 MOUNTAINEER-03 study (NCT03043313) and its effects in the CRC space.³ This trial assessed the safety and efficacy of frontline tucatinib and trastuzumab in patients with treatment-refractory, RASwild-type, HER2-positivemetastatic CRC. Primary endpoints for this analysis showed a clinically meaningful overall response rate of 38.1% and a median duration of response of 12.4 months. Additionally, the treatment combination was well tolerated.

She said she is “optimistic” that moving HER2-directed therapy to the first-line setting, as seen in the MOUNTAINEER-03 study, may help outcomes for patients with metastatic CRC.

“It’s a very exciting space,” Hubbard said. “Because it’s only 5% to 8% of patients [who have CRC], it may not get as much attention, but there’s 150,000 new cases of [CRC] diagnosed each year. So, 5% to 8% of that is a large number of patients [whom] we need to be looking at, studying, and potentially impact with these treatments.”

References

1. Yoshino T, Di Bartolomeo M, Raghav K, et al. Final results of DESTINY-CRC01 investigating trastuzumab deruxtecan in patients with HER2-expressing metastatic colorectal cancer. Nat Commun. 2023;14(1):1-13. doi:10.1038/s41467-023-38032-4
2. Seagen announces FDA accelerated approval of Tukysa (tucatinib) in combination with trastuzumab for people with previously treated RAS wild-type, HER2-positive metastatic colorectal cancer. News release. FDA. January 19, 2023. Accessed December 6, 2023. https://bwnews.pr/3Xpzbqn
3. 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. Published online January 24, 2023.doi:10.1200/jco.2023.41.4_suppl.tps261