Subcutaneous Amivantamab and Lazertinib in PALOMA-3: Efficacy, Safety, and Administration: A Vodcast

Intravenous (IV) amivantamab, an epidermal growth factor receptor (EGFR)-MET bispecific antibody, is approved for multiple indications alone or in combination for patients with EGFR-mutated advanced or metastatic nonsmall cell lung cancer (NSCLC). In the PALOMA-3 study, subcutaneous (SC) amivantamab was investigated to improve tolerability, reduce administration time, maintain efficacy, and improve patient experience. This vodcast reviews the rationale and data supporting SC amivantamab on the basis of the PALOMA-3 study and provides expert-led recommendations for SC amivantamab treatment. The PALOMA-3 study investigated the noninferiority of pharmacokinetics, with other endpoints including efficacy and safety of SC versus IV amivantamab, combined with lazertinib in participants with EGFR-mutated, advanced NSCLC after disease progression on osimertinib and platinum-based chemotherapy. Geometric mean ratios of C_trough for SC to IV amivantamab were 1.15 at Cycle 2 Day 1 (C2D1) and 1.42 at C4D1; C2_AUCD1-D15 was 1.035. Objective response rate (ORR) was 30% in the SC group and 33% in the IV group; median progression-free survival was 6.1 and 4.3 months, respectively. SC amivantamab resulted in fewer patients reporting infusion-related reactions (IRR; 13% versus 66% IV) and venous thromboembolism (VTE; 9% versus 14%) with prophylactic anticoagulation; shorter administration time at C1D1 (< 5 min per SC injection versus ~ 5 h for IV); and higher patient-reported convenience at the end of treatment (85% versus 35%). We discuss clinical considerations for SC amivantamab dosing and administration, including premedications, prophylactic measures, dose modifications, management of adverse reactions, and switching between IV and SC amivantamab. In conclusion, SC amivantamab demonstrated noninferior pharmacokinetics and antitumor responses compared with IV amivantamab in the PALOMA-3 study. SC amivantamab also reduced IRR and VTE, with shorter treatment administration times and enhanced patient convenience compared with IV. Utilizing SC amivantamab, while optimizing treatment efficacy and safety through mitigating and managing adverse events, may enhance the patient experience.