Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Multicenter Study
. 2024 Mar;19(3):500-506.
doi: 10.1016/j.jtho.2023.11.020. Epub 2023 Nov 25.

Real-World Efficacy and Safety of Amivantamab for EGFR-Mutant NSCLC

Kaiwen Wang  1 , Robyn Du  2 , Nathaniel J Myall  3 , Whitney E Lewis  1 , Natalie Uy  4 , Lingzhi Hong  2 , Ferdinandos Skoulidis  2 , Lauren A Byers  2 , Anne Tsao  2 , Tina Cascone  2 , Jenny Pozadzides  2 , Janet Tu  2 , Marcelo V Negrao  2 , Don L Gibbons  2 , Keunchil Park  2 , Waree Rinsurongkawong  2 , J Jack Lee  5 , David Gandara  6 , Deepti Behl  7 , Catherine A Shu  8 , Jonathan W Riess  6 , Christina Baik  4 , Heather A Wakelee  3 , Ara A Vaporciyan  9 , John V Heymach  2 , Jianjun Zhang  2 , Xiuning Le  10
Affiliations
Multicenter Study

Real-World Efficacy and Safety of Amivantamab for EGFR-Mutant NSCLC

Kaiwen Wang et al. J Thorac Oncol. 2024 Mar.

Abstract

Introduction: Amivantamab-vmjw (amivantamab) is a bispecific EGFR/MET antibody approved for patients with advanced NSCLC with EGFR exon 20 insertion mutations, after prior therapy. Nevertheless, the benefits and safety of amivantamab in other EGFR-mutant lung cancer, with or without osimertinib, and with concurrent radiation therapy, are less known.

Methods: We queried the MD Anderson Lung Cancer GEMINI, Fred Hutchinson Cancer Research Center, University of California Davis Comprehensive Cancer Center, and Stanford Cancer Center's database for patients with EGFR-mutant NSCLC treated with amivantamab, not on a clinical trial. The data analyzed included initial response, duration of treatment, and concomitant radiation safety in overall population and prespecified subgroups.

Results: A total of 61 patients received amivantamab. Median age was 65 (31-81) years old; 72.1% were female; and 77% were patients with never smoking history. Median number of prior lines of therapies was four. On the basis of tumor's EGFR mutation, 39 patients were in the classical mutation cohort, 15 patients in the exon 20 cohort, and seven patients in the atypical cohort. There were 37 patients (58.7%) who received amivantamab concomitantly with osimertinib and 25 patients (39.1%) who received concomitant radiation. Furthermore, 54 patients were assessable for response in the overall population; 19 patients (45.2%) had clinical response and disease control rate (DCR) was 64.3%. In the classical mutation cohort of the 33 assessable patients, 12 (36.4%) had clinical response and DCR was 48.5%. In the atypical mutation cohort, six of the seven patients (85.7%) had clinical response and DCR was 100%. Of the 13 assessable patients in the exon 20 cohort, five patients (35.7%) had clinical response and DCR was 64.3%. Adverse events reported with amivantamab use were similar as previously described in product labeling. No additional toxicities were noted when amivantamab was given with radiation with or without osimertinib.

Conclusions: Our real-world multicenter analysis revealed that amivantamab is a potentially effective treatment option for patients with EGFR mutations outside of exon 20 insertion mutations. The combination of osimertinib with amivantamab is safe and feasible. Radiation therapy also seems safe when administered sequentially or concurrently with amivantamab.

Keywords: Amivantamab; EGFR; NSCLC; Real-world analysis.

PubMed Disclaimer

Conflict of interest statement

Disclosure: Dr. Wang reports serving on the consulting/advisory board of BluPrint Oncology. Dr. Lewis reports serving on the consulting/ advisory board of Eisai, Takeda, and Bristol-Myers Squibb. Dr. Uy reports receiving travel grant for 2023 NCCN Oncology Fellows Program: New Horizons in Quality Cancer Care and NCCN 2023 Annual Conference. Dr. Skoulidis reports receiving research grants to institution from Revolution Medicines, Mirati Therapeutics, Pfizer, Merck, Amgen, and Novartis; serving on the consulting/advisory board of AstraZeneca, Amgen, Novartis, BeiGene, Guardant Health, Bergen Bio, Navire Pharma, Tango Therapeutics, Calithera Biosciences, Intellisphere LLC, and Medscape LLC; receiving honoraria from VSPO Mc Gill Universite de Montreal and RV Mais Promocao Eventos LTDS; receiving meeting support/travel grant from Amgen, Tango Therapeutics, and Dava Oncology; and having stock from Moderna and BioNTech SE. Dr. Byers reports receiving honoraria from UpToDate; having consulting or advisory role for Merck Sharp & Dohme Corp., Arrowhead Pharmaceuticals, Chugai Pharmaceutical Co., AstraZeneca, Genentech, AbbVie, BeiGene, Jazz Pharmaceuticals, Puma Biotechnology, Amgen, and Daiichi Sankyo; and receiving research funding to institution from AstraZeneca, Amgen, and Jazz Pharmaceuticals. Dr. Tsao reports receiving research funding to institution from Ariad, Bristol-Myers Squibb, Eli Lilly, Genentech, Millennium, Polaris, AstraZeneca, Boehringer Ingelheim, Epizyme, Merck, Novartis, and Seattle Genetics; serving on the consulting/advisory board of Ariad, Bristol-Myers Squibb, Eli Lilly, Genentech, Merck, Pfizer, Seattle Genetics, AstraZeneca, Boehringer Ingelheim, EMD Serono, GlaxoSmithKline, Novartis, and Roche. Dr. Cascone reports receiving speaker fees/honoraria from Society for Immunotherapy of Cancer (SITC), Mark Foundation for Cancer Research, Bristol-Myers Squibb, Roche, Medscape, IDEOlogy Health, Physicians’ Education Resource LLC (PER), OncLive, and PeerView; having consulting/advisory role from MedImmune/AstraZeneca, Bristol-Myers Squibb, Merck, Genentech, Arrowhead Pharmaceuticals, Pfizer Inc., and Regeneron; receiving travel, food, and/or beverage expenses from Physicians’ Education Resource LLC (PER), Dava Oncology, SITC, International Association for the Study of Lung Cancer, Parker Institute for Cancer Immunotherapy, IDEOlogy Health, OncLive, MedImmune/AstraZeneca, and Bristol-Myers Squibb; and receiving research funding to institution from MedImmune/AstraZeneca, Bristol-Myers Squibb, and EMD Serono. Dr. Negrao reports receiving research funding to institution from Mirati, Novartis, Checkmate, Alaunos, AstraZeneca, Pfizer, Genentech, and Navire; serving on the consultant/advisory board of Mirati, Merck/Merck Sharp & Dohme, Novartis, and Genentech; and receiving other support from Ziopharm Oncology, Apothecom, and Ashfield Healthcare. Dr. Gibbons reports receiving research funding to institution from AstraZeneca, Boehringer Ingelheim, NGM Biopharmaceuticals, Ribon Therapeutics, Mirati Therapeutics, and Astellas; serving on the consulting/advisory board of 4D Pharma, Onconova, Menarini Richerche, Eli Lilly, and AstraZeneca; and having leadership role from Rexanna’s Foundation for Fighting Lunca Cancer. Dr. Park reports serving on the Steering Committee of Johnson & Johnson. Dr. Gandara reports receiving honoraria from Amgen and Merck; having consulting or advisory role for Adagene, AstraZeneca, Daiichi Sankyo Alliance, Guardant Health, IO Biotech, Lilly, Novartis, Ocean Genomics, OncoCyte, OncoHost, Roche/Genentech, and Sanofi; and receiving research funding to institution from Amgen, AstraZeneca, Genentech, and Merck. Dr. Behl reports having consulting or advisory role for AstraZeneca, Bristol-Myers Squibb Foundation, Lilly, Novartis, Janssen Oncology, Novocure, and Taiho Pharmaceutical; serving on the speakers’ bureau of AstraZeneca. Dr. Shu reports serving on the consulting/advisory board of AstraZeneca, Arcus Biosciences, Genentech, Giles’s, Janssen, and Takeda. Dr. Riess reports serving on the consulting/advisory board of Blueprint, Beigene, Daiichi Sankyo, EMD Serono, Janssen, Regeneron, Sanofi, Biodesix, Bayer, Turning Point, Bristol-Myers Squibb, Jazz Pharmaceuticals, Novartis, Roche/Genentech, Boehringer Ingelheim, Merck, and SeaGen; receiving research funding to institution from Merck, Novartis, AstraZeneca, Spectrum, Revolution Medicines, Arrivent, IO Biotech, and Vitrac. Dr. Baik reports receiving research funding to institution from AbbVie, Rain Therapeutics, Nuvalent, Blueprint, Turning Point, Lilly, AstraZeneca, Janssen, Daiichi Sankyo, Spectrum, Pfizer, and Loxo; serving on the consulting/advisory board of Daiichi Sankyo, Boehringer, Janssen, Regeneron, Silverback, Pfizer, AstraZeneca, Guardant, Turning Point, and Takeda. Dr. Wakelee reports receiving research funding to institution from Bayer, AstraZeneca/Medimmune, Bristol-Myers Squibb, Clovis Oncology, Genentech/Roche, Merck, Novartis, SeaGen, Xcovery, and Helsinn; serving on the consulting/advisory board of Mirati, Merck, and Genentech/Roche; and having leadership roles as President of the International Association for the Study of Lung Cancer and member on the executive committee of ECOG-ACRIN. Dr. Heymach reports having stock and other ownership interests from Cardinal Spine and Bio-Tree; having consulting or advisory role from AstraZeneca, Bristol-Myers Squibb, Spectrum Pharmaceuticals, Guardant Health, Hengrui Pharmaceutical, GlaxoSmithKline, EMD Serono, Lilly, Takeda, Sanofi/Aventis, Genentech/Roche, Boehringer Ingelheim, Catalyst Biotech, Foundation medicine, Novartis, Mirati Therapeutics, Bright-Path Biotherapeutics, Janssen, Nexus Health Systems, Pneuma Respiratory, Kairos Ventures, Roche, and Leads Biolabs; receiving research funding to institution from AstraZeneca (Inst), Spectrum Pharmaceuticals, and GlaxoSmithKline; having patents, royalties, and other intellectual property on licensing agreement between Spectrum and MD Anderson (including myself) regarding intellectual property for treatment of EGFR and HER2 exon 20 mutations. Dr. Zhang reports serving on the consulting/advisory board of Bristol-Myers Squibb, AstraZeneca, Novartis, Johnson & Johnson, GenePlus, Innovent, Varian, and Catalyst; receiving research grants to institution from Merck, Novartis, and Johnson & Johnson. Dr. Le reports receiving consulting/advisory fees from EMD Serono (Merck KGaA), AstraZeneca, Spectrum Pharmaceutics, Novartis, Eli Lilly, Daiichi Sankyo, TAIHO, Boehringer Ingelheim, Hengrui Therapeutics, Janssen, Blueprint Medicines, Sensei Biotherapeutics, Abion, Regeneron, and AbbVie; receiving research funding to institution from Eli Lilly, EMD Serono, ArriVent, Teligene, Regeneron, and Boehringer Ingelheim. The remaining authors declare no conflict of interest.

Figures

Figure 1.
Figure 1.
Clinical response in patients receiving amivantamab w/osi or without osimertinib. CR, complete response; N, no; N/A, not applicable; PD, progressive disease; PR, partial response; SD, stable disease; w/osi: with osimertinib; Y, yes. *w/osi: with osimertinb
Figure 2.
Figure 2.
(A) Safety of amivantamab. (B) Scalp ulcerations of a patient on amivantamab monotherapy. Before starting dapsone (left). Post-dapsone (right).
See this image and copyright information in PMC

References

    1. Pao W, Chmielecki J. Rational, biologically based treatment of EGFR-mutant non-small-cell lung cancer. Nat Rev Cancer. 2010;10:760–774. - PMC - PubMed
    1. Tan AC, Tan DSW. Targeted therapies for lung cancer patients with oncogenic driver molecular alterations. J Clin Oncol. 2022;40:611–625. - PubMed
    1. Robichaux JP, Elamin YY, Tan Z, et al. Mechanisms and clinical activity of an EGFR and HER2 exon 20-selective kinase inhibitor in non-small cell lung cancer. Nat Med. 2018;24:638–646. - PMC - PubMed
    1. Robichaux JP, Le X, Vijayan RSK, et al. Structure-based classification predicts drug response in EGFR-mutant NSCLC. Nature. 2021;597:732–737. - PMC - PubMed
    1. Park K, Haura EB, Leighl NB, et al. Amivantamab in EGFR exon 20 insertion-mutated non-small-cell lung cancer progressing on platinum chemotherapy: initial results from the CHRYSALIS phase I study. J Clin Oncol. 2021;39:3391–3402. - PMC - PubMed

Publication types

MeSH terms