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Real-World Effectiveness of First-Line Osimertinib Versus Amivantamab-Based Regimens in EGFR-Mutated NSCLC: A Multicenter Comparative Outcome Study

Emily R. Thompson, Daniel J. Carter, Aisha M. RahmanORCID 1

1Department of Medical Oncology, The Royal Marsden NHS Foundation Trust, London, UK
2Lung Cancer Research Unit, University College London Hospitals (UCLH), London, UK
3Department of Cellular Pathology and Genomic Medicine, Oxford University Hospitals NHS Foundation Trust, Oxford, UK
DOI: 10.18081/ajbm.2025.4.330

Publication History: Received 24 August 2025, Revised 17 September 2025, Accepted 22 October 2025, Available online 13 November 2025
Copyright: © 2025 Rahman, et al. This is an open-access article under a Creative Commons license (CC BY 4.0).
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ABSTRACT

Background

Osimertinib is the established first-line standard of care for EGFR-mutated advanced non–small cell lung cancer (NSCLC); however, resistance—particularly via MET-driven pathways—remains a major clinical challenge. Amivantamab, a bispecific EGFR/MET antibody, has shown promising activity in early trials, but its real-world comparative effectiveness as first-line therapy remains unclear. This multicentre UK study evaluated clinical outcomes of first-line osimertinib versus amivantamab-based regimens in routine clinical practice.

Methods

This retrospective cohort study included adults with EGFR-mutated stage IIIB–IV NSCLC treated across five NHS tertiary oncology centres between 2019 and 2024. Patients received either osimertinib or an amivantamab-based regimen (monotherapy or in combination). The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival (OS), CNS progression, objective response, toxicity, and post-progression therapy. Multivariable Cox modelling and propensity score matching were performed.

Results

A total of 512 patients met eligibility criteria (osimertinib n=412; amivantamab-based n=100). Median PFS was significantly longer with amivantamab-based therapy (19.8 vs 16.2 months; HR 0.79, 95% CI 0.63–0.98; p=0.032), and remained significant after multivariable adjustment (HR 0.76, p=0.036). No significant OS difference was observed (33.7 vs 29.4 months; HR 0.90, p=0.48). ORR was similar between groups (74.0% vs 69.7%; p=0.41). CNS progression occurred in 12.0% of the amivantamab group versus 15.8% with osimertinib. Among patients with baseline CNS disease, time to intracranial progression favoured amivantamab (10.9 vs 8.4 months; p=0.19). Amivantamab was associated with higher rates of infusion-related and dermatological toxicities, while osimertinib displayed a more favourable tolerability profile.
Conclusion

In UK real-world practice, first-line amivantamab-based therapy demonstrated a clinically meaningful PFS advantage over osimertinib, particularly among patients with MET-associated biology, though OS differences were not yet evident. These findings support the emerging role of early dual EGFR/MET inhibition and highlight the importance of comprehensive molecular profiling to optimise first-line treatment selection. Longer follow-up and prospective studies are warranted to refine sequencing strategies and confirm survival impact.

Keywords: EGFR-mutated NSCLC, osimertinib, amivantamab, real-world evidence, progression-free survival, MET amplification.

Recommended Citation

Thompson E, Carter D, Rahman A. Real-World Effectiveness of First-Line Osimertinib Versus Amivantamab-Based Regimens in EGFR-Mutated NSCLC: A Multicenter Comparative Outcome Study. Advanced Journal of Biomedicine & Medicine. 2025;13(4):330-351. doi:10.18081/ajbm.2025.4.330

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This work is licensed under a Creative Commons Attribution 4.0 International License.

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Emily R. Thompson, Daniel J. Carter, Aisha M. Rahman (2025). Real-World Effectiveness of First-Line Osimertinib Versus Amivantamab-Based Regimens in EGFR-Mutated NSCLC: A Multicenter Comparative Outcome Study. American Journal of Biomedicine, 13(4), 330-351. https://doi.org/10.18081/ajbm.2025.4.330
Emily R. Thompson, Daniel J. Carter, Aisha M. Rahman. "Real-World Effectiveness of First-Line Osimertinib Versus Amivantamab-Based Regimens in EGFR-Mutated NSCLC: A Multicenter Comparative Outcome Study." American Journal of Biomedicine, vol. 13, no. 4, 2025, pp. 330-351. DOI: 10.18081/ajbm.2025.4.330.
Emily R. Thompson, Daniel J. Carter, Aisha M. Rahman. Real-World Effectiveness of First-Line Osimertinib Versus Amivantamab-Based Regimens in EGFR-Mutated NSCLC: A Multicenter Comparative Outcome Study. Am J Biomed. 2025;13(4):330-351. DOI: 10.18081/ajbm.2025.4.330. PMID: .
Emily R. Thompson, Daniel J. Carter, Aisha M. Rahman 2025, "Real-World Effectiveness of First-Line Osimertinib Versus Amivantamab-Based Regimens in EGFR-Mutated NSCLC: A Multicenter Comparative Outcome Study", American Journal of Biomedicine, vol. 13, no. 4, pp. 330-351.
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%0 Journal Article %A Emily R. Thompson, Daniel J. Carter, Aisha M. Rahman %T Real-World Effectiveness of First-Line Osimertinib Versus Amivantamab-Based Regimens in EGFR-Mutated NSCLC: A Multicenter Comparative Outcome Study %J American Journal of Biomedicine %V 13 %N 4 %P 330-351 %D 2025 %R 10.18081/ajbm.2025.4.330 %M
Emily R. Thompson, Daniel J. Carter, Aisha M. Rahman (2025). Real-World Effectiveness of First-Line Osimertinib Versus Amivantamab-Based Regimens in EGFR-Mutated NSCLC: A Multicenter Comparative Outcome Study. American Journal of Biomedicine, 13(4), 330-351. https://doi.org/10.18081/ajbm.2025.4.330

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