Trastuzumab deruxtecan (5) – Enhertu®

Non-small cell lung cancer, HER2(ERBB2) mutation, pre-treated

Characteristics

Start date 01.12.2023 – Marketing authorisation: 18.10.2023
Resolution 16.05.2024
INN Trastuzumab deruxtecan
Brand name Enhertu®
Pharm. company Daiichi Sankyo Deutschland GmbH
G-BA Procedure ID D-990
ATC code L01FD04 HER2 inhibitors (L01FD)
ICD-10 codes (AIS) C34.0Malignant neoplasm of carina, C34.1Malignant neoplasm of upper lobe, bronchus or lung, C34.2Malignant neoplasm of middle lobe, bronchus or lung, C34.3Malignant neoplasm of lower lobe, bronchus or lung, C34.8Malignant neoplasm of overlapping sites of bronchus and lung, C34.9Malignant neoplasm of unspecified part of bronchus or lung
Alpha-ID codes (AIS) I111155Carcinoma of the upper lobe bronchus, I116693Non-small cell lung cancer, I24595Carcinoma of the main bronchus, I30015Lung carcinoma of the middle lobe, I30021Lung carcinoma of the lower lobe, I30022Malignant neoplasm of the bronchi and lungs, overlapping several sub-areas
Therapeutic area Oncological diseases Non-small-cell lung carcinoma (NSCLC)
Reason for procedure New therapeutic indication
Regulatory status Conditional Approval

Therapeutic indication of the resolution

Enhertu is used as monotherapy for the treatment of adult patients with advanced NSCLC whose tumors have an activating HER2 (ERBB2) mutation and who require systemic therapy after platinum-based chemotherapy with or without immunotherapy.

Subpopulation Indication Comparator
a) Adults with advanced non-small cell lung cancer (NSCLC) whose tumors have an activating HER2 (ERBB2) mutation after prior treatment with platinum-containing chemotherapy without immunotherapy Docetaxel (only for patients with PD-L1 negative tumors) or – Pemetrexed (only for patients with PD-L1 negative tumors and except for predominantly squamous cell histology) or – nivolumab or – Pembrolizumab (only for patients with PD-L1 expressing tumors, Tumor Proportion Score (TPS) ≥ 1 %) or – Atezolizumab or – Docetaxel in combination with nintedanib (only for patients with PD-L1 negative tumors and adenocarcinoma histology)
b) Adults with advanced non-small cell lung cancer (NSCLC) whose tumors have an activating HER2 (ERBB2) mutation after prior treatment with a PD-1/PD-L1 antibody in combination with platinum-containing chemotherapy or after sequential therapy with a PD-1/PD-L1 antibody and platinum-containing chemotherapy - Docetaxel or – Docetaxel in combination with nintedanib (only for patients with adenocarcinoma histology) or – docetaxel in combination with ramucirumab or – pemetrexed (except for patients with predominantly squamous cell histology) or – vinorelbine (only for patients who are not suitable for docetaxel)

Studies and Results

No. of studies
(best subpopulation)
0 (Data not accepted)
Study design
(best subpopulation)
Data not accepted (Dossier: Single-arm + no comparison)
Reason for dividing into subpopulations (G-BA) Previous treatment

  • Clinical trials
    • The DESTINY-Lung02 trial is an ongoing, randomised, two-arm, double-blind, multicentre Phase II trial investigating the efficacy and safety of two different doses of trastuzumab deruxtecan (6.4 mg/kg vs. 5.4 mg/kg, once every three weeks) in adults with metastatic HER2-mutated NSCLC.

a) Adults with advanced non-small cell lung cancer (NSCLC) whose tumours harbour an activating HER2 (ERBB2) mutation, following prior treatment with platinum-based chemotherapy without immunotherapy

  • An additional benefit is not proven.
  • In the absence of direct comparative studies of trastuzumab deruxtecan against the appropriate comparator therapy, the pharmaceutical manufacturer cites the randomised, uncontrolled clinical study DESTINY-Lung02 as evidence of additional benefit.
  • Due to its single-arm design, the DESTINY-Lung02 study submitted by the pharmaceutical manufacturer does not allow for a comparison with the appropriate comparator therapy and is therefore not suitable for assessing the additional benefit of trastuzumab deruxtecan compared with the appropriate comparator therapy.

b) Adults with advanced non-small cell lung cancer (NSCLC) whose tumours harbour an activating HER2 (ERBB2) mutation, following prior treatment with a PD-1/PD-L1 antibody in combination with platinum-based chemotherapy or following sequential therapy with a PD-1/PD-L1 antibody and platinum-based chemotherapy

  • The additional benefit is not proven.
  • In the absence of direct comparative studies of trastuzumab deruxtecan against the appropriate comparator therapy, the pharmaceutical manufacturer cites the randomised, uncontrolled clinical study DESTINY-Lung02 as evidence of additional benefit.
  • The data submitted are not suitable for a comparison with the appropriate comparator therapy.

Courtesy translation only, please refer to the German original.

Associated procedures

Trastuzumab deruxtecan (7) Enhertu® Daiichi Sankyo Deutschland GmbH Oncological diseases HER2-positive adenocarcinoma of the stomach or the gastro-oesophageal junction, following trastuzumab-based therapy 360–600 100% Indication of minor additional benefit
Trastuzumab deruxtecan (6) Enhertu® Daiichi Sankyo Deutschland GmbH Oncological diseases Breast cancer, HR+, HER2-low or -ultralow, following at least one course of endocrine therapy 1,615–6,200 100% Hint for minor additional benefit
Trastuzumab deruxtecan (5) Enhertu® Daiichi Sankyo Deutschland GmbH Oncological diseases Non-small cell lung cancer, HER2(ERBB2) mutation, pre-treated 75–219 100% additional benefit not proven
Trastuzumab deruxtecan (3) Enhertu® Daiichi Sankyo Deutschland GmbH Oncological diseases Adenocarcinoma (AC) of the stomach or gastro-oesophageal junction, HER2-positive, after trastuzumab-based therapy 110–170
470–770
100% additional benefit not proven repealed subpopulations
Trastuzumab deruxtecan (4) Enhertu® Daiichi Sankyo Deutschland GmbH Oncological diseases Breast carcinoma (BC), HER2-low, pre-treated 1,350–4,700 100% Indication of considerable additional benefit
Trastuzumab deruxtecan (1) Enhertu® Daiichi Sankyo Deutschland GmbH Oncological diseases Breast carcinoma (BC), HER2+, after 1 prior therapy 3,370–3,750 100% Indication of non-quantifiable additional benefit
Trastuzumab deruxtecan (2) Enhertu® Daiichi Sankyo Deutschland GmbH Oncological diseases Breast carcinoma (BC), HER2+, at least 2 previous therapies 1,350–1,640 100% Indication of considerable additional benefit
start postponed Trastuzumab deruxtecan (8) Enhertu® Daiichi Sankyo Deutschland GmbH Oncological diseases Solid tumours, HER2+ (IHC3+), previously treated n.d. active procedure


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