Comparing Intensification Strategies and Toxicity Profiles

The panel contrasts FLAURA-2 (osimertinib plus chemotherapy) with MARIPOSA (osimertinib plus amivantamab), acknowledging similar efficacy profiles with overall survival approaching four years in both regimens. However, significant differences exist in toxicity profiles and supportive care requirements.

Dr. Camidge characterizes amivantamab as more time-intensive and supportive care-intensive, believing it represents a more toxic regimen than FLAURA-2 despite optimal supportive measures. His preference defaults to FLAURA-2 for intensification.

When asked about potential amivantamab frontline candidates, panelists identify limited scenarios: patients with baseline kidney disease precluding carboplatin, older patients with chemotherapy concerns, those philosophically opposed to chemotherapy, or patients with MET amplification or HER2 overexpression at baseline.

Dr. Lopes illustrates real-world amivantamab use with 2 cases: a patient with de novo MET amplification who specifically requested amivantamab after patient group discussions, and a second-opinion patient with initially negative liquid biopsy later found positive on more sensitive platforms, highlighting testing sensitivity variations.

Toxicity differences are substantial. FLAURA-2 combines osimertinib toxicity with manageable carboplatin-pemetrexed effects when proper supplementation is maintained. Amivantamab combinations produce both MET and EGFR-related toxicities, with skin toxicity proving particularly challenging despite intensive prophylaxis regimens. Time toxicity represents another significant consideration, as frequent clinic visits impact family time and quality of life. Financial toxicity also factors into decision-making, though less frequently discussed with patients than time-related burdens.