Non-small cell lung cancer, HER2-mutated

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

Page editor		Section editor
	Eric K. Singhi, MD MD Anderson Cancer Center Houston, TX, USA LinkedIn		Amit Kulkarni, MBBS University of Minnesota Minneapolis, MN, USA LinkedIn

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 PubMed

ESMO

• 2023: Hendriks et al. Oncogene-addicted metastatic non-small-cell lung cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up PubMed

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

1. 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

1. 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

1. 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 PubMed NCT03505710
2. 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 PubMed NCT04644237