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June 26, 2026

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

Key Points

This analysis aims to compare the outcomes of amivantamab plus chemotherapy versus chemotherapy alone in patients with EGFR-mutant NSCLC post-osimertinib.
Federated electronic health record network used for data extraction from 168 healthcare organizations.
1:1 propensity score matching was performed on demographics and clinical characteristics to balance cohorts.
Overall survival and safety were analyzed using risk analyses and Kaplan–Meier with log-rank tests.
Ami-chemo was associated with significantly lower mortality at 30.0% compared to 49.0% in the chemo group (p = 0.001).
Higher rates of venous thromboembolism (25.2% vs 14.0%, p = 0.032) and neutropenia (25.0% vs 13.3%, p = 0.013) were observed in ami-chemo group.
No significant difference in overall survival was noted, likely due to follow-up discrepancies.

Abstract

284 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. Outcome Ami-Chemo (%) Chemo (%) P HR (95% CI) Log-rank P Mortality 30.0 49.0 0.001 0.88 (0.60–1.30) 0.518 VTE 25.2 14.0 0.032 0.34 (0.18–0.65) 0.001 Neutropenia 25.0 13.3 0.013 0.42 (0.23–0.74) 0.002 Anemia 32.0 26.0 0.326 0.56 (0.34–0.93) 0.024 Thrombocytopenia 19.2 19.7 0.915 0.74 (0.42–1.33) 0.315 Nausea/vomiting 22.1 17.7 0.426 0.66 (0.36–1.23) 0.187 ED visits 18.6 12.5 0.303 0.41 (0.17–1.00) 0.043 Inpatient admits 40.8 40.0 0.936 0.64 (0.33–1.23) 0.178

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