Feb 2023: The Food and Drug Administration (FDA) has approved sacituzumab govitecan-hziy (Trodelvy, Gilead Sciences, Inc.) for people with hormone receptor (HR)-positive, HER2-negative (IHC 0, IHC 1+, or IHC 2+/ISH-) breast cancer that has spread to other parts of the body and can not be removed. These people have also had at least two other systemic therapies in a metastatic setting.
TROPiCS-02 (NCT03901339) was a multicenter, open label, randomized study that looked at how well a CDK 4/6 inhibitor, endocrine therapy, and a taxane worked in 543 women with HR-positive, HER2-negative breast cancer that had spread or could not be removed. The patients’ disease got worse after receiving any of these treatments. At least two previous chemotherapies were administered to patients with metastatic disease (one of which could be in the neoadjuvant or adjuvant setting if recurrence occurred within 12 months).
Patiënten werden gerandomiseerd (1:1) toegewezen aan chemotherapie als monotherapie (n = 271) of sacituzumab govitecan-hziy, 10 mg/kg als een intraveneus infuus, op dag 1 en 8 in een cyclus van 21 dagen. Voorafgaand aan de randomisatie selecteerde de onderzoeker een enkelvoudig chemotherapieregime uit een van de volgende opties: capecitabine (n=22), vinorelbine (n=63), gemcitabine (n=56) of eribuline (n=130). Eerdere chemotherapieregimes voor gemetastaseerde ziekte (2 vs. 3-4), viscerale metastase (ja of nee) en endocriene therapie in de gemetastaseerde setting gedurende ten minste 6 maanden werden allemaal gebruikt om randomisatie te stratificeren (ja of nee). Patiënten werden behandeld tot het begin van onaanvaardbare bijwerkingen.
Progression-free survival (PFS), as defined by a blinded independent central review in accordance with RECIST v1.1, served as the primary efficacy outcome measure. Overall survival was a crucial secondary efficacy outcome metric (OS). The median PFS for the sacituzumab govitecan-hziy arm was 5.5 months (95% CI: 4.2, 7.0) and for the single agent chemotherapy arm was 4 months (95% CI: 3.1, 4.4) (hazard ratio [HR] of 0.661 [95% CI: 0.529, 0.826]; p-value=0.0003). For those getting sacituzumab govitecan-hziy, the median OS was 14.4 months (95% CI: 13.0, 15.7), whereas for those receiving single agent chemotherapy, it was 11.2 months (95% CI: 10.1, 12.7) (HR of 0.789 [95% CI: 0.646, 0.964]; p-value=0.0200).
Verminderd aantal leukocyten (88%), verminderd aantal neutrofielen (83%), verlaagd hemoglobine (73%), verlaagd aantal lymfocyten (65%), diarree (62%), vermoeidheid (60%), misselijkheid (59%), alopecia (48%), verhoogde glucose (37%), obstipatie (34%) en verlaagd albumine (32%) waren de meest voorkomende bijwerkingen (25%) bij patiënten die werden behandeld met sacituzumab govitecan-hziy in TROPiCS-02.
On Days 1 and 8 of a 21-day therapy cycle, 10 mg/kg of sacituzumab govitecan-hziy should be infused intravenously once a week until the disease gets worse or the side effects become too much to handle, whichever comes first.
Project Orbis, an initiative of the FDA Oncology Center of Excellence, was used to carry out this review. Using the infrastructure that Project Orbis provides, international partners can submit and review oncology medications simultaneously. FDA worked together on this review with the Therapeutic Goods Administration (TGA) of Australia, Health Canada, and Swissmedic. At the other regulatory organizations, the application reviews are still proceeding.
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