Managing Subcutaneous Amivantamab Toxicities in Head and Neck Cancer

Subcutaneous amivantamab-vmjw (Rybrevant Faspro) presents a distinct adverse effect (AE) profile in head and neck cancer, requiring proactive, coordinated management from the multidisciplinary care team. According to Barbara Burtness, MD, although the transition to the subcutaneous formulation significantly reduces the risk and severity of drug administration-related reactions, limiting events to grade 1 or 2, clinicians must remain vigilant for class effects associated with EGFR and MET inhibition.

She explained that EGFR-driven dermatologic toxicities mirror those seen with agents like cetuximab (Erbitux), making familiar strategies such as topical steroids, sunscreen, and oral tetracyclines central to management. Conversely, Burtness expressed that MET inhibition introduces challenges like hypoalbuminemia and soft tissue edema. In patients with head and neck cancer, prior surgical or radiation interventions heighten the risk of facial edema, rendering early collaboration with lymphedema specialists essential. Maintaining optimal protein intake and nutritional support remains crucial to mitigate mechanism-based protein loss. Ultimately, cross-specialty communication ensures these predictable toxicities are managed effectively without compromising treatment continuity.

Burtness is a medical oncologist and Anthony N. Brady Professor of Medicine (Medical Oncology) at Yale Cancer Center in New Haven, Connecticut. She is also the chief translational research officer, chief of Head and Neck Cancers/Sarcoma, co-leader of Developmental Therapeutics, and associate cancer center director for Translational Research at Yale Cancer Center.

Transcript:

All toxicities seen with subcutaneous amivantamab were previously known from other studies with subcutaneous amivantamab, and they are predominantly class effects of EGFR inhibition and MET inhibition, with the addition of hypersensitivity reactions to the drug itself. Whereas those had been potentially severe with the intravenous formulation, [they are not] with the subcutaneous formulation; in this trial, there was a 15% rate of drug administration-related reactions, and all of those were grade 1 and 2. There were no grade 3 reactions. In terms of the skin reaction, it is not too dissimilar from a cetuximab reaction, so an approach with topical steroids, sunscreen, and oral minocycline or doxycycline, if it becomes more severe, will feel very familiar to most care teams.

In terms of MET toxicity, you are looking at hypoalbuminemia and some soft tissue edema. There are 2 components to that. One is to do everything you can to maintain albumin, protein intake, and nutritional status, which can sometimes be a little fraught in [patients with head and neck cancer] anyway. The second thing is soft tissue edema. To your point about aftereffects of prior chemotherapy or radiation, there is a greater risk for facial edema here, maybe [more so] than in [patients with lung cancer]. Working closely with your lymphedema team and helping the patient understand how nutrition and facial edema can be linked through the mechanism of protein loss are the mainstays.