Real-World Outcomes With Sacituzumab Govitecan Match ASCENT in Single-Center Study

Data from the ASCENT trial (NCT02574455) led to the approval of sacituzumab govitecan-hziy (Trodelvy) for patients with metastatic triple-negative breast cancer (TNBC) in 2021.¹ However, real-world outcomes for the agent have not been reported, according to Sabah Alaklabi, MBBS, and investigators, at Roswell Park Comprehensive Cancer Center in Buffalo, New York.

In a single-center study based at the institution, investigators assessed real-world outcomes in patients with metastatic TNBC treated with the antibody-drug conjugate (ADC). An additional objective was to assess these outcomes in those with HER2-low disease.²

Twenty-four patients were treated, and 18 patients responded to treatment. The overall response rate was 61.1%; the partial response rate was 61.1%. The median duration of response was 6.5 months (range, 3-13). Stable disease was reported among 22.2% of patients and 16.7% had disease progression.2

The median progression-free survival was 5.1 months (95% CI, 2.5-7.2) and the median overall survival was 11.6 months (95% CI, 4.5-16.3).

Adverse effects (AEs) were observed at the following rates: nausea/vomiting (66.7%), fatigue (60.9%), diarrhea (50.0%), febrile neutropenia (50.0%), neutropenia (41.7%), mucositis (20.8%), alopecia (16.7%), and anemia (4.2%). Treatment discontinuations due to AEs were reported for 2 patients (8.7%) and 14 patients (60.9%) had toxicities that resulted in dose reductions.

“Metastatic TNBC is a complex disease with limited therapeutic options and is associated with a poor prognosis,” Alaklabi, a hematology/oncology fellow at Roswell Park, and colleagues wrote in the poster presented at the 40th Annual Miami Breast Cancer Conference^®. “The treatment landscape for TNBC has expanded in the [past] few years, but the optimal sequencing of agents after first-line therapy remains unclear.”

The retrospective analysis examined patients treated from January 1, 2021, to December 31, 2022. At baseline, demographic and clinical characteristics were collected, with HER2 status being evaluated by immunohistochemistry (IHC).²

The median age was 58 years (range, 29-84) and most patients had an ECOG performance status of 1 (58.3%) or 0 (33.3%). One patient each had an ECOG performance status of 2 and 3. The common sites of metastases included liver (66.7%), bone (66.7%), lung (45.8%), brain (29.2%), lymph nodes (29.2%), or other (4.2%). At the time of receiving sacituzumab govitecan, most patients had received at least 3 prior therapies (75.0%). Prior therapies included a taxane (70.8%), PD-1/PD-L1 inhibitor (58.3%), capecitabine (45.8%), an anthracycline (25.0%), endocrine therapy (13.0%), PARP inhibitor (12.5%), and carboplatin (8.3%).²

Nearly all patients had TNBC (91.7%) with 2 patients (8.3%) having hormone receptor–positive disease. Three patients had BRCA1/2-positive disease. In terms of HER2 IHC score, 79.2% of patients had IHC 1+ or 2+ disease and 20.8% of patients had IHC 0 disease.²

Most patients received sacituzumab govitecan at the recommended starting dose of 10 mg/kg (87.5%), with the remainder of the cohort starting the ADC at 7.5 mg/kg (8.3%) or 5 mg/kg (4.2%). The median relative dose intensity was 80%.²

“In our heavily pretreated metastatic TNBC population, sacituzumab govitecan produced comparable disease response, tolerability, and patients received a similar relative dose intensity [to ASCENT],” the authors wrote.

In ASCENT, patients were randomly assigned to sacituzumab govitecan or single-agent chemotherapy. The primary trial population for efficacy did not include individuals with brain metastases.

“Similar to the ASCENT trial our cohort included heavily pretreated patients with a median of 3 lines of prior therapy, which included immunotherapy and PARP inhibitors,” the authors wrote. “In contrast to the ASCENT trial, which excluded patients with brain metastases, approximately 30% [n = 7] of our cohort had brain metastases and comparable clinical outcomes.”

The primary trial population for efficacy did not include individuals with brain metastases. Among patients who received chemotherapy (n = 233), the investigators mostly selected eribulin (54%) followed by vinorelbine (20%), capecitabine (13%), and gemcitabine (12%).³

In the primary efficacy population, the median PFS for those who received sacituzumab govitecan (n = 235) was 5.6 months (95% CI, 4.3-6.3) vs 1.7 months (95% CI, 1.5-2.6) with chemotherapy (n = 233; HR, 0.41; 95% CI, 0.32-0.52; P < .001).3 Among all randomized patients, the median PFS for patients receiving sacituzumab govitecan (n = 267) was 4.8 months (95% CI, 4.1-5.8) compared with 1.7 months (95% CI, 1.5-2.5) in those receiving chemotherapy (n = 262; HR, 0.43; 95% CI, 0.35-0.54; P < .001). The median OS was 11.8 months (95% CI, 10.5-13.8) vs 6.9 months (95% CI, 5.9-7.6), respectively (HR, 0.51; 95% CI, 0.41-0.62; P < .001).³

Response in the HER2-low subgroup was notable, the investigators wrote, “given that [patients with] HER2-low [disease] were not yet recognized as a clinically relevant subgroup in the ASCENT trial and in light of what is now known about the efficacy of fam-trastuzumab deruxtecan-nxki [Enhertu] in patients with HER2-low metastatic breast cancer.”

The authors concluded by noting that a multi-institutional collaboration is ongoing to increase the sample size and overcome the limitations of this study.

References

1. FDA grants regular approval to sacituzumab govitecan for triple-negative breast cancer. News release. FDA. April 8, 2021. Accessed March 2, 2023. https://www.fda.gov/drugs/resources-information-approved-drugs/
2. Alaklabi S, Elijah E, Roy AM, Groman A, Gandhi S. Real world outcomes of sacituzumab govitecan in metastatic breast cancer patients: a single institution experience. Poster presented at: 40th Annual Miami Breast Cancer Conference; March 2-5, 2023; Miami Beach, FL.
3. Bardia A, Hurvitz SA, Tolaney SM, et al; ASCENT Clinical Trial Investigators. Sacituzumab govitecan in metastatic triple-negative breast cancer. N Engl J Med. 2021;384(16):1529-1541. doi:10.1056/NEJMoa2