Frontline Shifts, VEGF Inhibition, and Bispecific Antibodies

Balazs Halmos, MD, raises the French PERSEE trial, in which chemoimmunotherapy outperformed immunotherapy alone in non-small cell lung cancer (NSCLC) with high programmed death ligand 1 (PD-L1) expression. Vamsidhar Velcheti, MD, already uses chemoimmunotherapy for most of these patients and reserves programmed cell death protein 1 (PD-1) monotherapy for low disease and symptom burden. Alexander Spira, MD, PhD, FACP, says the result shows how limited PD-L1 is as a biomarker and stresses that many patients never reach second-line therapy, so frontline choices matter. On vascular endothelial growth factor (VEGF) inhibition, Dr. Velcheti finds the REVEL data encouraging; however, he avoids ramucirumab in squamous disease because of cavitary lesions and hemoptysis risk. Dr. Spira does not use ramucirumab given its modest benefit and cost, and he sees anti-angiogenesis returning through PD-1 and VEGF bispecific antibodies such as ivonescimab. He says growing HARMONi data, including some from the United States, suggest it works, with better patient selection easing earlier squamous safety concerns.