Real-world effectiveness and safety of amivantamab plus chemotherapy versus chemotherapy alone in EGFR-mutant NSCLC after osimertinib: A propensity score–matched analysis.

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Background: Amivantamab plus carboplatin–pemetrexed was approved (Sep 2024) for EGFR-mutant advanced NSCLC post-osimertinib, based on MARIPOSA-2 PFS data (HR 0.48). OS has not reached significance in trial interim analyses, and real-world data remain limited. We compared outcomes of amivantamab-chemotherapy (ami-chemo) versus chemotherapy alone (chemo) post-osimertinib using a federated electronic health record network. Methods: Using the TriNetX Global Collaborative Network (168 healthcare organizations), we identified adults with EGFR-mutant NSCLC (ICD-10 C34.x) and prior osimertinib who received ami-chemo (index: amivantamab with platinum within 30 days) or chemo alone (index: platinum, excluding amivantamab within 30 days). 1:1 propensity score matching balanced cohorts on age, sex, race, Charlson comorbidities, metastatic sites (brain, bone, liver), and labs (albumin, hemoglobin, creatinine, LDH). OS and safety were assessed via risk analysis and Kaplan–Meier with log-rank testing. Results: After matching, 151 pairs were analyzed (median follow-up: ami-chemo 201 vs chemo 365 days). Key outcomes are in the Table. Conclusions: Ami-chemo was associated with significantly lower mortality (30.0% vs 49.0%; p = 0.001) versus chemo alone, though KM-OS was non-significant, likely reflecting asymmetric follow-up. Ami-chemo showed significantly higher VTE and neutropenia, consistent with MARIPOSA-2 trial data. These findings provide early real-world evidence supporting ami-chemo effectiveness post-osimertinib while confirming the need for proactive toxicity management.