Non-small cell lung cancer, HER2-mutated

Back to Top
Note: these are regimens tested in biomarker-specific populations, please see the main NSCLC page for other regimens.
There are several related dedicated pages:
*Histology-specific:
**NSCLC, Nonsquamous
**NSCLC, Squamous
*Site-specific:
**NSCLC, CNS metastases
Last updated on 2024-07-23:3 regimens on this page
4 variants on this page
=Guidelines=
Given the rapid change in evidence in many areas of hematology/oncology, readers are encouraged to consider any guideline published 5+ years ago to be for historical purposes, only.
==ASCO==
*2022: Singh et al. Therapy for Stage IV Non-Small-Cell Lung Cancer With Driver Alterations: ASCO Living Guideline EuroPMC
==ESMO==
*2024: Lee et al. Pan-Asian adapted ESMO Clinical Practice Guidelines for the diagnosis, treatment and follow-up of patients with oncogene-addicted metastatic non-small-cell lung cancer EuroPMC
*2023: Hendriks et al. Oncogene-addicted metastatic non-small-cell lung cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up EuroPMC
==NCCN==
*NCCN does not currently have guidelines at this granular level; please see NCCN Guidelines - Non-Small Cell Lung Cancer.
=Metastatic disease, all lines of therapy=
==Carboplatin, Pemetrexed, Pembrolizumab==
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator	Comparative Efficacy
Awaiting publication (DESTINY-Lung04)	2021-ongoing 	Phase 3 (C)	T-DXd 	TBD if different primary endpoint of PFS
====Chemotherapy====
*Carboplatin (Paraplatin)
*Pemetrexed (Alimta)
====Immunotherapy====
*Pembrolizumab (Keytruda)
===References===
#DESTINY-Lung04: NCT05048797
==Cisplatin, Pemetrexed, Pembrolizumab==
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator	Comparative Efficacy
Awaiting publication (DESTINY-Lung04)	2021-ongoing 	Phase 3 (C)	T-DXd 	TBD if different primary endpoint of PFS
====Chemotherapy====
*Cisplatin (Platinol)
*Pemetrexed (Alimta)
====Immunotherapy====
*Pembrolizumab (Keytruda)
===References===
#DESTINY-Lung04: NCT05048797
==Trastuzumab deruxtecan monotherapy==
===Regimen variant #1, 5.4 mg/kg===
FDA-recommended dose
Study 	Dates of enrollment	Evidence
Goto et al. 2023 (DESTINY-Lung02)	2021-03 to 2022-03 	Phase 2 (RT)
====Biomarker eligibility criteria====
*HER2 mutations
====Antibody-drug conjugate therapy====
*Trastuzumab deruxtecan (Enhertu) 5.4 mg/kg IV once on day 1
21-day cycles
===Regimen variant #2, 6.4 mg/kg===
Study 	Dates of enrollment	Evidence
Li et al. 2021 (DESTINY-Lung01) 	2018-2020 	Phase 2
Goto et al. 2023 (DESTINY-Lung02)	2021-03 to 2022-03 	Phase 2
====Biomarker eligibility criteria====
*HER2 mutations
====Antibody-drug conjugate therapy====
*Trastuzumab deruxtecan (Enhertu) 6.4 mg/kg IV once on day 1
21-day cycles
===References===
#DESTINY-Lung01: Li BT, Smit EF, Goto Y, Nakagawa K, Udagawa H, Mazières J, Nagasaka M, Bazhenova L, Saltos AN, Felip E, Pacheco JM, Pérol M, Paz-Ares L, Saxena K, Shiga R, Cheng Y, Acharyya S, Vitazka P, Shahidi J, Planchard D, Jänne PA; DESTINY-Lung01 Trial Investigators. Trastuzumab Deruxtecan in HER2-Mutant Non-Small-Cell Lung Cancer. N Engl J Med. 2022 Jan 20;386(3):241-251. Epub 2021 Sep 18. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article EuroPMC NCT03505710
#DESTINY-Lung02: Goto K, Goto Y, Kubo T, Ninomiya K, Kim SW, Planchard D, Ahn MJ, Smit EF, de Langen AJ, Pérol M, Pons-Tostivint E, Novello S, Hayashi H, Shimizu J, Kim DW, Kuo CH, Yang JC, Pereira K, Cheng FC, Taguchi A, Cheng Y, Feng W, Tsuchihashi Z, Jänne PA. Trastuzumab Deruxtecan in Patients With HER2-Mutant Metastatic Non-Small-Cell Lung Cancer: Primary Results From the Randomized, Phase II DESTINY-Lung02 Trial. J Clin Oncol. 2023 Nov 1;41(31):4852-4863. Epub 2023 Sep 11. Erratum in: J Clin Oncol. 2023 Dec 19;:JCO2302574. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors EuroPMC NCT04644237
Category:Non-small cell lung cancer regimens
Category:Biomarker-specific pages
Category:Non-small cell lung cancers