Subcutaneous Amivantamab: Default First-Line or One of Three?

Panelists agreed that subcutaneous amivantamab represents meaningful progress over the IV formulation, nearly eliminating infusion reactions, reducing dosing frequency to every four weeks, and lowering high-grade dermatologic toxicity, although grade 1-2 rash and the burden of the COCOON prophylaxis regimen remain relevant considerations for patients. There was consensus that simplifying the patient experience around prophylaxis, framing it as three manageable medications rather than an overwhelming regimen, and involving dedicated pharmacy support are key to keeping patients on therapy. However, panelists pushed back on the premise of a single first-line default, with the closing argument that all three regimens (amivantamab-lazertinib, osimertinib-chemotherapy, and osimertinib monotherapy) represent valid standards of care, with the optimal choice driven by shared decision-making around patient goals, mutation profile, CNS status, and tolerance for toxicity.