Optimizing the Treatment Experience — COCOON, Counseling, and Anticoagulation

Drs. Goldberg and Nagasaka turn to the practical side of optimizing tolerability with amivantamab plus lazertinib. Dr. Nagasaka notes that prophylactic management is far more effective than reactive management. Her clinic built an EPIC order set so the multi-component COCOON regimen can be ordered with a single click, and she finds starter kits and early dermatology referral materially reduce patient burden. For centers without a dedicated dermatology partner, she recommends initiating referrals earlier given typical insurance approval timelines. Dr. Goldberg agrees that higher-grade dermatologic toxicities still occur but are now mostly manageable, and that she escalates promptly to dose interruption or reduction when needed rather than continuing maximal supportive care indefinitely.

On peripheral edema related to MET inhibition, Dr. Nagasaka finds it less severe than with classical MET inhibitors but persistent and bothersome for some patients. Standard measures — compression stockings, leg elevation, and salt restriction — help, but diuretics are generally unhelpful for this MET-driven edema. In her experience, dose interruption and occasionally dose reduction are the most effective tools. On prophylactic anticoagulation, Dr. Nagasaka prefers direct oral anticoagulants because they are easier for patients than low-molecular-weight heparin. She notes that the 13% venous thromboembolism rate observed in cohort 5 should be interpreted against a baseline rate of 5% to 10% in metastatic NSCLC, and that prophylactic dosing rarely produces bleeding. For most patients she continues prophylaxis past the protocol-defined 4-month window rather than stopping at month 4.

In the next episode, "Summary — Putting It All Together for 1L EGFRm NSCLC," Dr. Nagasaka recaps the four key dimensions of the regimen and closes the program.