TP53 Co-Mutation and First-Line Regimen Selection

Matthew Gumbleton, MD, PhD, of Huntsman Cancer Institute rejects the idea that a TP53 co-mutation points toward chemotherapy in epidermal growth factor receptor (EGFR)-mutated advanced non–small cell lung cancer (NSCLC). Estelamari Rodriguez, MD, MPH, of Sylvester Comprehensive Cancer Center presents median progression-free survival of approximately 18 months with amivantamab plus lazertinib versus 12.9 months with osimertinib in patients with TP53 co-mutations, with better outcomes in both arms among patients with wild-type TP53. Dr Gumbleton says TP53 marks more aggressive disease across tumor types and deserves an intensified regimen, but because he already treats lung cancer as high risk, it rarely changes his recommendation on its own. He cautions that these are exploratory subgroup analyses that can move the needle at the margin without being decisive. Siddhartha Devarakonda, MD, of Providence Swedish Cancer Institute adds that he watches for MET amplification as an under-recognized driver.