Treatment Options after Disease Progression in Metastatic Colorectal Cancer

Jaclyn Hechtman, MD: What treatment options are available for this patient if and when they progress?

Andrea Cercek, MD: After first-line therapy with FOLFOX [5-fluorouracil, leucovorin, oxaliplatin] and bevacizumab, you would then initiate trastuzumab plus pertuzumab. That's our HER2 [human epidermal growth factor receptor 2]-targeted therapy in the second-line setting. Following that we still have the chemotherapy backbone of FOLFIRI [leucovorin, fluorouracil, irinotecan], which is an active combination and should be utilized after progression on HER2-targeted therapy. There are 2 other approved oral agents, regorafenib and TAS-102 [tipiracil hydrochloride], which can be used, but of course, we need to think about potential clinical trials as well. Clinical trials are always an important thing to keep in mind. Most likely for this patient, it would be after progression on FOLFIRI. For most trials, you need progression on 2 lines of cytotoxic chemotherapy, but not always. If the patient is a fit for a clinical trial, they should be considered, but those are kind of our standard options. Then, in terms of further HER2-targeted therapy, that's limited—but hopefully something that will continue to develop over time and will have better targets, but fam-trastuzumab deruxtecan is an antibody-drug conjugate composed of an anti-HER2 antibody and sort of this linker to a topoisomerase 1 inhibitor. It was studied in patients who were exposed to prior HER2 therapy and showed some promising responses even in those patients who were previously exposed to HER2 targeting because it just works by a different mechanism.I think that could then potentially be a target or a combination that's utilized for this patient as well.

Transcript edited for clarity.