Redefining First-Line EGFR+ NSCLC with Subcutaneous Amivantamab & Lazertinib

At the 2026 European Lung Cancer Congress (ELCC), Dr Nicolas Girard discussed updated data from the PALOMA-2 study, which evaluates the subcutaneous (SC) formulation of amivantamab (Rybrevant) in combination with lazertinib (Lazcluze) for the first-line treatment of EGFR-mutated advanced non-small cell lung cancer (NSCLC).

Efficacy and Durability

Dr Girard highlighted that the PALOMA-2 regimen mirrors the Mariposa trial (which used intravenous [IV] amivantamab) but demonstrates potentially improved efficacy outcomes. In a cohort of 68 patients, the combination yielded a high objective response rate of 85%. Notably, the median progression-free survival (PFS) reached 27.6 months—numerically higher than that reported in Mariposa—with an overall survival rate of nearly 90% at 18 months. Girard suggested that the improved safety profile of the SC formulation may lead to better treatment adherence and, consequently, prolonged efficacy.

Safety and Administration Advantages

The transition from IV to SC administration offers several clinical advantages:

• Reduced Administration Time: The SC injection takes only five minutes, significantly reducing the time patients spend in the clinic compared to IV infusions.
• Improved Tolerability: The SC formulation virtually eliminates infusion-related reactions, which are common with IV amivantamab.
• Prophylactic Success: The study implemented mandatory prophylactic anticoagulation for the first four months, resulting in only one venous thromboembolism (VTE) event among 68 patients. Girard also noted the importance of preemptive dermatological management to mitigate cutaneous side effects.

Clinical Outlook

Dr Girard emphasized that this "chemo-free" regimen represents a new standard of care, offering an alternative to osimertinib (Tagrisso) or chemo-combination therapies. Because it is easier to administer and has a manageable safety profile, Girard envisions SC amivantamab becoming the preferred delivery method, potentially moving toward home-based administration in the future. By intensifying first-line treatment with this combination, clinicians can preserve chemotherapy for subsequent lines of therapy, optimizing the overall patient journey.