Dr. Goldberg reviews the safety and tolerability profile of subcutaneous amivantamab Q4W plus lazertinib in PALOMA-2 cohort 5 and the proactive strategies developed to support patients on therapy. She walks through the most common treatment-emergent adverse events occurring in 20% or more of patients, grouped by mechanism. EGFR-related events included paronychia (73%), rash (58%), dermatitis acneiform (40%), stomatitis (38%), pruritus (34%), and diarrhea (29%). MET-related events included hypoalbuminemia (64%) and peripheral edema (36%), with no grade 3 or higher edema observed. Other events included elevated ALT, elevated AST, and dry skin. Only 8% of patients discontinued all study treatment because of treatment-related adverse events. The administration-related reaction rate was 12%, with 1% grade 3 or higher and 78% occurring at the first injection — roughly 5-fold lower than with intravenous administration. Grade 3 or higher bleeding occurred in 1%.
Dr. Goldberg then turns to proactive management. The COCOON regimen — oral doxycycline or minocycline in weeks 1 through 12, clindamycin scalp lotion in weeks 13 through 52, chlorhexidine 4% nail wash daily, and a ceramide-based moisturizer daily — reduced moderate to severe dermatologic events from 75% to 42% in the COCOON trial. Prophylactic anticoagulation in months 1 through 4 with a direct oral anticoagulant or low-molecular-weight heparin was used by 87% of cohort 5 patients; the resulting venous thromboembolism rate was 13%, with no grade 3 or higher events and no related dose reductions, discontinuations, or deaths. Dose modifications occurred in 59% of MARIPOSA patients without compromising progression-free survival.
In the next episode, “Optimizing the Treatment Experience — COCOON, Counseling, and Anticoagulation,” Drs. Goldberg and Nagasaka share clinic-level workflows for putting this into practice.
