Sacituzumab Govitecan Granted Regular FDA Approval for mTNBC

The FDA granted a regular approval to sacituzumab govitecan (Trodelvy) for the treatment of patients with unresectable locally advanced or metastatic triple-negative breast cancer (mTNBC) who have received two or more prior systemic therapies, at least one of them for metastatic disease, according to a press release from the agency.¹

This FDA action follows an accelerated approval granted for the drug in 2020 based on data from the phase 3 ASCENT study (NCT0257445) in which patients 529 were randomized 1:1 to receive either sacituzumab govitecan or treatment of physician’s choice. Sacituzumab govitecan was administered at a dose of 10 mg/kg and treatment continued until disease progression or unacceptable toxicity. The study demonstrated improvement in progression-free survival (PFS) and overall survival (OS) improvement with Sacituzumab govitecan compared with standard of care chemotherapy in pretreated patients with mTNBC, meeting the primary end point and one of the secondary end points of the study.

In addition to PFS and OS, the study also explored objective response rate, duration of response, and time to onset of response.

In all patients who were randomized in the study, including the brain metastases population, Sacituzumab govitecan lead to a median PFS of 4.8 months (95% CI, 4.1-5.8) compared with 1.7 months (95% CI, 1.5-2.5) in patients who received chemotherapy (HR, 0.43; 95% CI: 0.35-0.54; P <.0001). In addition, the median OS was 11.8 months (95% CI, 10.5-13.8) with sacituzumab govitecan compared with 6.9 months (95% CI, 5.9-7.6) with chemotherapy (HR 0.51; 95% CI, 0.41, 0.62; P <.0001).

Sacituzumab govitecan also achieved an ORR of 35% in patients with mTNBC versus 5% for with physician’s choice of therapy (P <.0001).

In the 482 patients who received at least one dose of any treatment in the study, treatment-related grade ≥3 adverse events (AEs) were observed. The most common treatment-related grade ≥3 AEs in the ADC arm versus the physician’s choice arm were neutropenia (51% vs 33%), diarrhea (10.5% vs <1%), anemia (8% vs 5%), and febrile neutropenia (6% vs 2%).²

Other common AEs associated with sacituzumab govitecan treated include nausea, , diarrhea, fatigue, alopecia, vomiting, constipation, rash, decreased appetite, and abdominal pain.¹

Subgroup analysis data of 61 patients with brain metastases were also in favor of sacituzumab govitecan. The group had a median age of 53 years (range, 27-80) in the sacituzmab govitecaan arm versus 51 years (range, 34-81) in the control arm. Most of the patients in both arms were White with an ECOG performance status of 1 and no BRCA1/2 mutations. The median number of prior regimens was 5 (range, 2-10), and a total of 43% had received prior checkpoint inhibition.³

In the brain metastasis population, the ORR was 3% with sacituzumab govitecan compared with 0% with chemotherapy, and the disease control rates were 9% and 3%, respectively. The analysis also showed stable disease (SD) in 47% and 31% in Sacituzumab govitecan and chemotherapy arms, respectively, but SD was not long-lasting.

In terms of survival, the median PFS was 2.8 months (95% CI, 1.5-3.9) with sacituzumab govitecan and 1.6 months (95% CI, 1.3-2.9) with chemotherapy (HR, 0.65; 95% CI, 0.35-1.22). At 3 months, the PFS rate was 41.4% with the ADC and 27.7% with chemotherapy. By 9 months the corresponding PFS rates were 9.0% and 0%.

In addition, a modest difference in OS was observed between the 2 study arms. The median OS was 6.8 months (95% CI, 4.7-14.1) with sacituzumab govitecan and 7.5 months (95% CI, 4.7-11.1) with physician’s choice of treatment (HR, 0.87; 95% CI, 0.47-1.63).

_References:

_{1. FDA grants regular approval to sacituzumab govitecan for triple-negative breast cancer. News release. FDA. April 7, 2021. Accessed April 7, 2021. https://bit.ly/3dJu7Yr}

_{2. Bardfia A, Tolaney SM, Loirat D, et al. LBA17 - ASCENT: A randomized phase III study of sacituzumab govitecan (SG) vs treatment of physician’s choice (TPC) in patients (pts) with previously treated metastatic triple-negative breast cancer (mTNBC). Ann Oncol. 2020;30 (suppl 4): S1142-S1215. doi: 10.1016/annonc/annonc325}

_{3. Diéras V, Weaver R, Tolaney SM, et al. Subgroup analysis of patients with brain metastases from the phase 3 ASCENT study of sacituzumab govitecan versus chemotherapy in metastatic triple-negative breast cancer. Presented at: 2020 San Antonio Breast Cancer Symposium; December 8-11, 2020. Abstract PD13-04.}