Dr Foote on the Ongoing Debate Over Upfront EGFR Inhibitor Use in CRC

“I’m using [EGFR inhibitors] more and more up front now for my patients, especially if they’re young and they're healthy, and especially if I think we need a [to achieve a] big response that enables something else, like surgery. If they have a lot of symptoms from their cancer, and I want to shrink it quickly to make them feel better, then I would include EGFR inhibitors in my frontline [treatment approach]."

Michael Foote, MD, medical oncologist, assistant attending physician, Memorial Sloan Kettering Cancer Center, discusses the ongoing debate regarding the use of EGFR inhibitors in the frontline setting or in subsequent lines of therapy for patients with metastatic colorectal cancer (CRC).

The phase 3 PARADIGM study (NCT02394795) demonstrated that using the EGFR inhibitor panitumumab (Vectibix) in the first-line treatment of patients with RAS wild-type, left-sided CRC provides a survival benefit of 3.6 months compared with standard first-line therapy. However, only approximately half of the patients in the panitumumab and bevacizumab arms went on to receive subsequent treatment with bevacizumab and panitumumab, respectively. For example, 41.8% of the patients in the control arm who received chemotherapy plus bevacizumab (Avastin) did not subsequently receive an EGFR inhibitor, despite evidence from other studies confirming their survival benefit, Foote reports. This raises questions about whether the observed benefit with panitumumab would remain if all patients had received the agent in subsequent lines of therapy, he states.

A practical challenge in real-world treatment settings is that patients may become too ill to tolerate subsequent therapy, underscoring the importance of administering effective treatments earlier in the disease course, Foote notes. Delivering EGFR inhibitors upfront can ensure patients receive this active therapy, as delaying treatment may render some patients ineligible due to disease progression or declining performance status, Foote says.

Globally, many oncologists incorporate EGFR inhibitors into the first-line setting for patients with RAS wild-type, left-sided tumors, particularly when a strong response is needed for symptom control or to enable surgical intervention, Foote continues. However, concerns about adverse effects, such as rash, and the lack of definitive evidence that upfront use is superior, lead some centers to reserve EGFR inhibitors for later lines of therapy, he explains. Ultimately, the decision is individualized, with factors such as patient age, health status, tumor burden, and treatment goals influencing the choice, Foote says. Increasingly, younger and healthier patients, or those requiring a robust response, are considered candidates for upfront EGFR inhibitor use, he concludes.