The Federal Joint Committee (G-BA) had specified chemotherapy with capecitabine or vinorelbine or eribulin or, if necessary, a therapy containing anthracycline or taxane as appropriate comparator therapy.
IQWiG sees a hint of a major added benefit of sacituzumab govitecan compared to the appropriate comparator therapy. The effects in overall survival were decisive for this positive assessment: In the intervention group, the median survival time of patients was 11.8 months compared to 6.7 months in the control group.
Breast cancer is divided into subtypes based on how many estrogen receptors and progesterone receptors or human epidermal growth factor receptors 2 (HER2) are present on the surface of the cancer cells. All three receptors are known to promote the growth of breast cancer. Drugs that block their activity are a mainstay of breast cancer treatment.
Triple-negative breast cancer has low levels of all three receptors. This eliminates essential targets for tumor therapy. About 15 to 20% of all breast carcinomas are triple-negative. Triple-negative breast cancer involves a high risk of metastasis and recurrence and a poor prognosis. It occurs mainly in young women.
However, in triple-negative breast cancer, there are high concentrations of a protein called trop-2. This is where the antibody-drug conjugate sacituzumab govitecan comes in: The antibody component is supposed to bind directly to trop-2 on the surface of the cancer cell.
When the antibody (sacituzumab) and trop-2 interact, the entire antibody-drug conjugate is drawn into the cancer cell. Inside the cell, the drug linked to the antibody, the chemotherapeutic agent SN-38 (govitecan), is then released to kill the cancer cell.
Overall: hint of a major added benefit
IQWiG’s early benefit assessment is based on the ASCENT study. ASCENT is an open-label, randomized controlled trial with a total of 529 included patients for whom, according to the inclusion criteria, monotherapy with capecitabine, vinorelbine, eribulin, or gemcitabine should be suitable. Gemcitabine is not part of the appropriate comparator therapy.
Therefore, only the subpopulation of 445 patients for whom capecitabine, eribulin, or vinorelbine was chosen as therapy is relevant for the dossier assessment. Due to ambiguities in the evaluation, the risk of bias of the study and its outcomes was high so that no more than hints of greater benefit or harm can be derived from the results.
ASCENT study showed more positive than adverse effects of sacituzumab govitecan compared to the appropriate comparator therapy:
In particular, IQWiG sees a hint of a major added benefit in the study outcome “overall survival” (11.8 months in the intervention group versus 6.7 in the control group). Moreover, treatment with sacituzumab govitecan causes fewer side effects.
In terms of symptoms, the positive effects predominate: Although patients experience diarrhea more often, this is offset by benefits in terms of pain and respiratory disorders.
For the health-related quality of life, only advantages of sacituzumab govitecan are shown compared to the appropriate comparator therapy. However, the effects observed for side effects, symptoms, and health-related quality of life refer exclusively to the period until the end of treatment (plus 30 days) and not until the end of the study or the time point of death.
In summary, IQWiG sees a hint of a major added benefit of sacituzumab govitecan compared with the appropriate comparator therapy for adult patients with non surgically removable or metastatic triple-negative breast cancer have previously received two or more systemic therapies, including at least one for advanced disease.
G‑BA decides on the extent of added benefit
The dossier assessment is part of the early benefit assessment according to the Act on the Reform of the Market for Medicinal Products (AMNOG) supervised by the G-BA. After the publication of the dossier assessment, the G-BA conducts a commenting procedure and makes a final decision on the extent of the added benefit.