KEY TAKEAWAYS:
- Anti-EGFR therapies (panitumumab and cetuximab) commonly cause skin toxicities such as rash and nail changes that, while not life-threatening, can significantly impact quality of life. Preemptive management with the STEPP regimen—moisturizer, sunscreen, topical steroid, and doxycycline—is key.
- Bevacizumab’s antiangiogenic mechanism increases the risk of hypertension, delayed wound healing, and gastrointestinal perforation. A 6-week washout period before surgery is recommended, and the presence of stents is generally a contraindication due to elevated perforation risk.
- Cetuximab can cause infusion reactions linked to geographic exposure to tick bites. Monitoring for hypomagnesemia during anti-EGFR therapy is important, and initiating amiloride early can help manage electrolyte loss.
As part of the Tox Check series, Rahul Gosain, MD, MBA, and Rohit Gosain, MD, met with Pashtoon Kasi, MD, MS, of City of Hope, to discuss the best ways to manage adverse effects of the anti-VEGF antibody bevacizumab and 2 anti-EGFR antibodies, panitumumab and cetuximab.
All 3 agents are key in the treatment of metastatic colorectal cancer and other gastrointestinal tumors that, “in most scenarios, are added to a backbone of chemotherapy to make it more effective and to help prolong survival,” Dr. Kasi said.
Adverse Effects of Bevacizumab
Due to bevacizumab’s mechanism of action affecting vasculature, the primary toxicities include delay in wound healing, hypertension, proteinuria, risk of bleeding or thrombosis, and a small risk of perforation. Given the impact on wound healing, a washout period of around 6 weeks is needed before any major procedures, whether or not they’re related to the cancer.
“It’s about good communication between the patients and other caregivers and specialties that might be taking care of them,” Dr. Kasi suggested. “For example, if somebody is undergoing liver or colon surgery, we would hold the bevacizumab 6 weeks prior to allow for no issues with wound healing or fistulas or other issues that might happen.”
Notably, a stent is often considered a total contraindication to starting anti-VEGF treatment because the risk of perforation rises from about 2% to 5% to as high as 25% or more, according to Dr. Kasi.
Due to bevacizumab’s mechanism of action, elevated blood pressure occurs in almost every patient, so adequate home monitoring and planning for new or worsening hypertension are imperative. Regarding thromboembolic risk, Dr. Kasi referenced the Khorana score as a tool to inform potential use of anticoagulation prior to starting systemic therapy.
Adverse Effects of Panitumumab
For panitumumab, the doctors highlighted primary adverse effects including skin toxicities, nail effects, and electrolyte imbalances. “While none of these toxicities at first glance look medically life-threatening, these can be disabling and a major quality-of-life issue if not controlled well,” Dr. Kasi said. “I’ve had patients that would pick absolutely anything but going on anti-EGFR treatment again because the first time around they had such a bad rash.”
However, Dr. Kasi did qualify that—similar to high blood pressure with anti-VEGF treatment—rash is to be expected with anti-EGFR therapies given the mechanism of action, and some studies even associated rash with improved survival.
The cutaneous toxicity can be managed preemptively with a regimen described in the STEPP study. The protocol consists of daily moisturizers, sunscreen, and steroid cream, plus 100 mg of doxycycline twice a day. Sun avoidance is also recommended. Dr. Kasi suggested that patients see a dermatologist to manage rash while on anti-EGFR treatment. He also noted that the antibiotics can be stopped and started as rash symptoms come and go.
Adverse Effects of Cetuximab
As an anti-EGFR therapy, cetuximab, too, can cause skin toxicities but is also associated with unique infusion-site reactions. This adverse effect is seen in geographic areas where tick bites can lead to the development of IgE antibodies against cetuximab, so knowing where a patient lives or grew up can have bearing on treatment choice.
Notably, for colorectal cancers, Dr. Kasi pointed out that biweekly dosing of cetuximab is as effective as weekly dosing and also aligns with intravenous chemotherapy administration. Dr. Kasi recommended starting with full dosing unless dealing with a geriatric patient population.
In a similar vein, the IMPROVE trial evaluated intermittently stopping anti-EGFR treatment after a few months of chemotherapy backbone. The intermittent schedule reduced the severity of cumulative skin and other quality-of-life issues without compromising the primary end point of progression-free survival.
Hypomagnesemia, another relevant adverse effect of panitumumab and cetuximab, develops after 2 or 3 treatment cycles.
For a final clinical pearl, Dr. Kasi highlighted use of the potassium-sparing diuretic amiloride: “I make sure every single patient of mine who is on anti-EGFR starts it once a day the moment they start showing even low-normal numbers.”
