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. 2025 Mar 31;14(3):707-717.
doi: 10.21037/tlcr-24-617. Epub 2025 Mar 20.

Amivantamab as a salvage therapy post-EGFR-tyrosine kinase inhibitor failure in patients with mutated EGFR non-small cell lung cancer

Bilal Krayim #  1 , Waleed Kian #  1 , Maria Spector  2 , Inbal Granot  1 , Julia Dudnik  3 , Michal Nissim  3 , Dolev Kahala  1 , Areen Abu Remilah  1 , Naama R Bogot  2 , Gleb Kornev  1 , Noam Asna  1 , Nir Peled  1 , Laila C Roisman  1
Affiliations

Amivantamab as a salvage therapy post-EGFR-tyrosine kinase inhibitor failure in patients with mutated EGFR non-small cell lung cancer

Bilal Krayim et al. Transl Lung Cancer Res. .

Abstract

Background: Amivantamab is an approved dual epidermal growth factor receptor (EGFR) and mesenchymal-epithelial transition (MET) inhibitor for the treatment of EGFR exon 20 insertion (EGFRex20ins) mutations. Recent data support the use of amivantamab for both common and uncommon EGFR mutations after previous therapies. In this study, we investigated the role of adding amivantamab to the ongoing EGFR-tyrosine kinase inhibitor (TKI) in later lines of therapy upon progression.

Methods: Patients treated at Shaare Zedek Medical Center (SZMC) from October 2021 to May 2024 who received amivantamab plus a previous EGFR-TKI. Cohort A included nine patients with common EGFR mutations [four exon 19 deletions (ex19dels), one G719C, four L858R]. Cohort B included six patients with exon 20 insertions. Safety and preliminary efficacy were evaluated according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.

Results: In cohort A, the objective response rate (ORR) was 22% (L858R 50%, exon 19 0%), disease control rate (DCR) 44% (L858R 100%, exon 19 0%), median duration of treatment (mDoT) 3 months (L858R 7.5 months, exon 19 2.3 months), and median overall survival (mOS) 6.7 months (L858R 14.4 months, exon 19 4.6 months). In cohort B, ORR was 17%, DCR 83%, mDoT 5.5 months, and mOS 16.2 months. Grade ≥3 toxicities included nausea, diarrhea, rash, infusion reactions, and thromboembolism.

Conclusions: This pilot study suggests that adding late-line amivantamab to an ongoing EGFR-TKI may have potential benefits in selected non-small cell lung cancer (NSCLC) patients with EGFR mutations, but resulted in high skin toxicity. Patients with EGFR L858R mutations appeared to show improved responses to amivantamab compared to the lack of response with ex19dels, while acquired resistance was associated with loss of the original EGFR driver mutation and MET alterations. However, these preliminary findings lack robust evidence due to study limitations, and larger, prospective, multi-center trials are needed to validate these results.

Keywords: Epidermal growth factor receptor (EGFR); amivantamab; exon 20 insertion; non-small cell lung cancer (NSCLC); tyrosine kinase inhibitor (TKI).

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Conflict of interest statement

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-24-617/coif). L.C.R. serves as an unpaid editorial board member of Translational Lung Cancer Research from February 2024 to January 2026. W.K. declares receiving lecture fees from MSD, Bristol-Myers Squibb, Pfizer, and AstraZeneca. These affiliations have no influence on the content or conclusions of his research, publications, or professional activities. N.P. receives consulting fees/payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Eli Lilly, Imagine, Gaurdant360, Imagene, Merck, MSD, Novartis, Pfizer, Roche, Rhenium, and Takeda; holds stock or stock options from Imagine; and is chairman of the Israeli Lung Cancer Foundation and Member of the Board of Directors. L.C.R. receives grants from EU Horizon 2020 and Thermo Fisher Oncomine and is an IASLC member of the basic and translational committee and I3Lung executive board member. The other authors have no conflicts of interest to declare.

Figures

Figure 1
Figure 1
Swimmer plot showing treatment duration, best overall responses and outcomes for each patient. Cohort A included nine patients with common EGFR mutations (four ex19dels, one G719C, four L858R). Cohort B included six patients with exon 20 insertions. Ex19dels, exon 19 deletions; PD, progressive disease; PR, partial response; SD, stable disease.
Figure 2
Figure 2
Adverse events to amivantamab of a cohort B patient. (A,B) Severe paronychia; (C) rash on the scalp exhibiting signs of an infection with pus.
See this image and copyright information in PMC

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