Trastuzumab deruxtecan (4) – Enhertu®
Breast carcinoma (BC), HER2-low, pre-treated
Characteristics
| Start date | 01.02.2023 – Marketing authorisation: 23.01.2023 |
|---|---|
| Resolution | 20.07.2023 |
| INN | Trastuzumab deruxtecan |
| Brand name | Enhertu® |
| Pharm. company | Daiichi Sankyo Deutschland GmbH |
| G-BA Procedure ID | D-905 |
| ATC code | L01FD04 HER2 inhibitors (L01FD) |
| ICD-10 codes (AIS) | C50.0Malignant neoplasm of nipple and areola, C50.1Malignant neoplasm of central portion of breast, C50.2Malignant neoplasm of upper-inner quadrant of breast, C50.3Malignant neoplasm of lower-inner quadrant of breast, C50.4Malignant neoplasm of upper-outer quadrant of breast, C50.5Malignant neoplasm of lower-outer quadrant of breast, C50.6Malignant neoplasm of axillary tail of breast, C50.8Malignant neoplasm of overlapping sites of breast, C50.9Malignant neoplasm of breast of unspecified site |
| Alpha-ID codes (AIS) | I102868Malignant neoplasm of the outer 2 quadrants of the mammary gland, I102970Malignant neoplasm of the upper inner quadrant of the mammary gland, I102971Malignant neoplasm of the lower inner quadrant of the mammary gland, I102972Malignant neoplasm of the upper outer quadrant of the mammary gland, I102973Malignant neoplasm of the lower outer quadrant of the mammary gland, I102998Malignant neoplasm of the central glandular body of the mammary gland, I102999Malignant neoplasm of the axillary recess of the mammary gland, I111628Malignant neoplasm of the nipple and areola, I18060Metastatic breast cancer |
| Therapeutic area | Oncological diseases Mammary carcinoma / Breast cancer (BC) |
| Reason for procedure | New therapeutic indication |
| Regulatory status | Conditional Approval |
| Specialty | Bundling Special practice conditions |
| Therapeutic indication of the resolution |
|---|
|
Enhertu is used as monotherapy for the treatment of adult patients with unresectable or metastatic HER2-low breast cancer who have already received chemotherapy in the metastatic setting or who have had a recurrence during or within 6 months of completion of adjuvant chemotherapy. |
| Subpopulation | Indication | Comparator |
|---|---|---|
| Adults with unresectable or metastatic HER2-low breast cancer who have already received chemotherapy in the metastatic setting or who have had a recurrence during or within 6 months after completion of adjuvant chemotherapy | Capecitabine or - eribulin or - vinorelbine or - anthracycline- or taxane-containing therapy (only for patients who have not yet received anthracycline- and/or taxane-containing therapy or who are eligible for renewed anthracycline- or taxane-containing treatment) |
Studies and Results
|
No. of studies
(best subpopulation) |
1 (DESTINY-Breast04) |
|---|---|
|
Study design
(best subpopulation) |
H2H vs. ACT |
|
Meta analysis
(best subpopulation) |
no |
- Clinical trials
- DESTINY-Breast04 is a multicentre, open-label, randomised controlled trial comparing trastuzumab deruxtecan with treatment as the clinician deems appropriate, selected from capecitabine, eribulin, gemcitabine, paclitaxel or nab-paclitaxel.
Adults with inoperable or metastatic HER2-low breast cancer who have already received chemotherapy for their metastatic disease or who have experienced a recurrence during or within 6 months of completing adjuvant chemotherapy
- Consequently, the G-BA has determined that trastuzumab deruxtecan offers an indication of a considerable additional benefit compared with capecitabine, eribulin, paclitaxel or nab-paclitaxel.
- Consequently, the certainty of the evidence for the established additional benefit is classified as ‘indication’.
- mortality
- For the endpoint of overall survival, a statistically significant prolongation of survival was observed in the relevant patient population following treatment with trastuzumab deruxtecan compared with capecitabine, eribulin, paclitaxel or nab-paclitaxel, the extent of which is assessed as a marked improvement.
- For this endpoint, there was an effect modification by the characteristic ‘visceral disease (yes/no)’. A statistically significant advantage in favour of trastuzumab deruxtecan was observed for both patients with visceral disease and those without visceral disease.
- In the overall assessment of the available results from the DESTINY-Breast04 trial, this effect modification by the characteristic ‘visceral disease’ is not considered sufficient to derive separate conclusions regarding additional benefit in the overall evaluation.
- Morbidity – Progression-free survival (PFS)
- In the relevant patient population, a statistically significant prolongation of PFS was observed in favour of trastuzumab deruxtecan compared with capecitabine, eribulin, paclitaxel or nab-paclitaxel.
- The PFS endpoint is a composite endpoint comprising endpoints from the categories of mortality and morbidity. The ‘mortality’ component of the endpoint is already assessed as a standalone endpoint via the ‘overall survival’ endpoint. The ‘disease progression’ component of morbidity is not assessed on the basis of symptoms, but exclusively by means of imaging procedures (radiologically determined disease progression according to the RECIST 1.1 criteria). Taking the above aspects into account, there are differing views within the G-BA regarding the clinical relevance of the PFS endpoint to patients. This does not affect the overall assessment of the extent of the additional benefit.
- Morbidity – Symptoms
- In the analysis of the time to first deterioration by ≥ 10 points, a statistically significant advantage in favour of trastuzumab deruxtecan was observed for the relevant patient population for the endpoints of pain and insomnia.
- For the endpoints of nausea and vomiting, as well as diarrhoea, statistically significant differences were observed between the treatment groups, with a disadvantage for trastuzumab deruxtecan.
- No suitable data are available for the endpoint of distress caused by hair loss. For all other endpoints, no statistically significant difference was observed between the treatment groups.
- Taking the results as a whole, no overall advantage or disadvantage was identified with regard to symptoms.
- Morbidity – Health status
- No statistically significant difference was observed between the treatment groups for the health status endpoint.
- With regard to health status, therefore, trastuzumab deruxtecan has neither positive nor negative effects.
- Health-related quality of life
- In the analysis of time to first deterioration of ≥ 10 points, a statistically significant advantage in favour of trastuzumab deruxtecan was observed for the relevant patient population for the endpoints of physical functioning, cognitive functioning, social functioning and body image.
- No suitable data are available for the endpoint ‘enjoyment of sex’. For all other endpoints, no statistically significant difference was observed between the treatment groups.
- Overall, trastuzumab deruxtecan offers advantages in terms of quality of life.
- Side effects – Serious adverse events (SAEs)
- For serious adverse events, a statistically significant advantage in favour of trastuzumab deruxtecan was observed in the relevant patient population.
- Side effects – Severe AEs (CTCAE grade ≥ 3)
- For severe adverse events with a CTCAE grade of ≥ 3, a statistically significant advantage was observed in favour of trastuzumab deruxtecan in the relevant patient population.
- Side effects – Discontinuation due to AEs
- For the endpoint ‘discontinuation due to AEs’, there was no statistically significant difference between the treatment groups.
- Overall assessment
- For the endpoint of overall survival, treatment with trastuzumab deruxtecan showed a statistically significant prolongation of survival compared with capecitabine, eribulin, paclitaxel or nab-paclitaxel, which is considered a marked improvement.
- With regard to symptoms (assessed using the EORTC QLQ-C30 and -BR23), an overall review of the results reveals no predominant advantage or disadvantage of trastuzumab deruxtecan. With regard to health status (assessed using the EQ-5D VAS), neither positive nor negative effects were observed.
- In terms of quality of life (assessed using the EORTC QLQ-C30 and -BR23), trastuzumab deruxtecan offers advantages over capecitabine, eribulin, paclitaxel or nab-paclitaxel.
- In terms of side effects, trastuzumab deruxtecan showed advantages with regard to serious AEs and severe AEs. With regard to therapy discontinuations due to AEs, there were no statistically significant differences between the treatment groups. In detail, both advantages and disadvantages of trastuzumab deruxtecan as an AEs are evident with regard to specific AEs.
- Overall, the G-BA concludes that, particularly in view of the significant positive effects on prolonging survival and given the advantages in terms of quality of life and side effects, trastuzumab-deruxtecan is recommended for the treatment of adult patients with inoperable or metastatic HER2-low breast cancer who have already received chemotherapy for metastatic disease or who have experienced a recurrence during or within 6 months of completing adjuvant chemotherapy, offers considerable additional benefit compared with capecitabine, eribulin, paclitaxel or nab-paclitaxel.
Courtesy translation only, please refer to the German original.
Associated procedures
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