Expert Explains Safety of Krazati Regimen For Treating Colorectal Cancer

Krazati plus Erbitux is well tolerated in KRAS G12C-mutant metastatic colorectal cancer, with manageable side effects and less immune suppression.

Treatment with Krazati (adagrasib) plus Erbitux (cetuximab) demonstrated meaningful efficacy in heavily pretreated patients with KRAS G12C–mutant unresectable or metastatic colorectal cancer, according to phase 1/2 KRYSTAL-1 trial data presented at the 2025 ASCO Gastrointestinal Cancers Symposium.

Dr. Nataliya Uboha is a medical oncologist at UW Health, as well as an associate professor and researcher in the Department of Medicine at the University of Wisconsin School of Medicine and Public Health, and shared her insights on the trial in an interview with CURE.

Glossary:

Overall response rate: the percentage of patients who have a complete or partial response to a treatment.

Disease control rate: the percentage of patients who have a complete, partial or stable response to a cancer treatment.

At a median follow-up of 20.4 months, the overall response rate was 34% by blinded independent central review and 43% by investigator assessment. Disease control rates were 85% and 86%, respectively.

In the interview, Uboha sat down to discuss the KRYSTAL-1 study and highlighted what makes Krazati combined with Erbitux safe when compared to other treatment regimens such as Vectibix.

Transcript:

This a very important question, because when we give treatments to our patients, even if the treatment is very active, if it has a lot of side effects, it is hard to deliver these treatments, or harder for patients to tolerate. The good news is that this regimen is pretty well tolerated. We are seeing some gastrointestinal side effects, in particular nausea, so some patients will need to take anti-nausea medications before taking Krazati [adagrasib].

We've seen a little bit of diarrhea as well with the anti-EGFR drugs that are already approved for colorectal cancer. Notably, Erbitux [cetuximab], Vectibix [panitumumab] are notorious for causing rashes, but we’ve not seen as much of a rash with these drugs when we combine them with Krazati [adagrasib] in the study, but this is something else to look for. In contrast to chemotherapy, these agents do not cause significant suppression in the immune system, so that's the differentiating side effect between this combination and chemotherapy.

Transcript has been edited for clarity and conciseness.

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