Sacituzumab govitecan extends survival regardless of Trop-2 expression in breast cancer
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SAN ANTONIO — Sacituzumab govitecan prolonged survival compared with physician’s choice of therapy among patients with heavily pretreated breast cancer, according to results presented at San Antonio Breast Cancer Symposium.
Findings from a post-hoc analysis of the TROPiCS-02 trial — which included patients with hormone receptor-positive, HER2-negative advanced disease — showed benefit with sacituzumab govitecan (Trodelvy, Gilead) regardless of Trop-2 expression, leading researchers to conclude that Trop-2 testing is not required for treatment with the agent.
Background and methods
As Healio previously reported, the randomized phase 3 TROPiCS-02 study included 543 patients with ECOG performance status of 0 or 1 who had received two to four prior lines of chemotherapy and at least one line of endocrine therapy for metastatic breast cancer.
Researchers randomly assigned patients 1:1 to sacituzumab govitecan (n = 272), dosed at 10 mg/kg IV on days 1 and 8 every 21 days, or physician’s choice of treatment (n = 271). Physician’s choice options included capecitabine, eribulin, vinorelbine or gemcitabine.
Treatment continued until disease progression or unacceptable toxicity.
PFS by blinded independent central review served as the primary endpoint. OS, response, duration of response, safety and quality of life served as secondary endpoints.
The primary analysis showed median PFS of 5.5 months with sacituzumab govitecan vs. 4 months with physician’s choice (HR = 0.66; 95% CI, 0.53-0.83).
Results of the second planned interim analysis showed median OS of 14.4 months with sacituzumab govitecan vs. 11.2 months with physician’s choice (HR = 0.79; P = .02).
Results
At SABCS, Hope S. Rugo, MD, professor of medicine and director of breast oncology and clinical trials education at UCSF Helen Diller Comprehensive Cancer Center presented data on efficacy outcomes by Trop-2 expression.
This analysis included 238 patients assigned sacituzumab govitecan and 224 assigned physician’s choice.
Most patients (95%) had tumors with Trop-2 H-scores above 0l; in this group, 42% had H-scores less than 100 and 58% had H-scores of 100 or higher.
Median follow-up was 10.2 months for PFS and 12.5 months for OS.
Researchers reported longer median PFS with sacituzumab govitecan among those with H-scores less than 100 (5.3 months vs. 4 months; HR = 0.77; 95% CI, 0.54-1.09), as well as those with H-scores of 100 or higher (6.4 months vs. 4.1 months; HR = 0.6; 95% CI, 0.44-.81).
Researchers also reported longer median OS with sacituzumab govitecan among those with H-scores less than 100 (14.6 months vs. 11.3 months), as well as those with H-scores of 100 or higher (14.4 months vs. 11.2 months; HR = 0.83; 95% CI, 0.62-1.11).
Researchers reported objective response rates with sacituzumab govitecan of 24% among those with H-scores 10 or lower, 18% among those with H-scores of 10 to 99, and 23% among those with H-scores 100 or higher.
The agent exhibited a safety profile consistent with prior reports, according to researchers.
Perspective
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Steven J. Isakoff, MD, PhD
Since its initial approval in 2020 for metastatic triple-negative breast cancer, sacituzumab govitecan has made a critical impact on improving OS. At ASCO earlier this year, we saw the first results of the TROPiCS-02 study showing a significant improvement in PFS compared with physician choice’s of treatment in metastatic hormone receptor-positive breast cancer. An updated analysis presented at ESMO Congress showed an OS improvement.
Sacituzumab govitecan is an antibody-drug conjugate that includes an antibody to the cell surface target TROP2 linked to the chemotherapy payload SN38, a topoisomerase-1 inhibitor. The level of TROP2 on the cell surface varies across breast cancer, and it was unknown if the activity of the agent correlated with Trop-2 expression. Previous data from the phase 3 ASCENT study in triple-negative breast cancer showed sacituzumab govitecan was active across all TROP2 levels. Similar results are now reported in the TROPiCS-02 study. These data are very reassuring that TROP2 testing is not necessary when considering sacituzumab govitecan for metastatic hormone receptor-positive breast cancer. Further, it shows sacituzumab govitecan is not really a targeted therapy in the traditional sense, but is a very effective chemotherapy delivery system.
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Rugo H, et al. Abstract GS5-11. Presented at: San Antonio Breast Cancer Symposium; Dec. 6-10, 2022.
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