The latest analysis of the TROPiCS-02 breast cancer trial showed that the antibody-drug conjugate sacituzumab govitecan-hziy is effective in patients with a wide range of Trop-2 expression levels. The findings were reported at the 2022 San Antonio Breast Cancer Symposium by Hope S. Rugo, MD, FASCO, Professor of Medicine and Director of Breast Oncology and Clinical Trials Education at the University of California San Francisco Helen Diller Family Comprehensive Cancer Center.1
“There was no clear level of Trop-2 expression at which a better treatment effect for sacituzumab govitecan was observed.”— Hope S. Rugo, MD, FASCO
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“This post hoc analysis demonstrated that sacituzumab govitecan improves outcomes in patients with pretreated, endocrine-resistant, hormone receptor–positive, HER2-negative metastatic breast cancer regardless of Trop-2 expression…. Trop-2 testing is not required for treatment,” Dr. Rugo said.
High Trop-2 expression is observed in breast cancer regardless of the subtype. Sacituzumab govitecan is a Trop-2–directed antibody-drug conjugate approved for pretreated metastatic triple-negative breast cancer. It has been evaluated in patients with hormone receptor–positive disease in the phase III TROPiCS-02 study, where it significantly improved progression-free survival (hazard ratio [HR] = 0.66; P < .0003)2 and overall survival (HR = 0.79; P = .02)3 compared with treatment of physician’s choice.
“We conducted an exploratory analysis to evaluate the potential impact of Trop-2 expression on efficacy outcomes in TROPiCS-02. Trop-2 expression was not required to determine patient eligibility and was not a stratification factor,” Dr. Rugo said.
The 543 patients had hormone receptor–positive, HER2-negative, locally recurrent, inoperable or metastatic breast cancer. They were previously treated with at least one taxane, endocrine agent, and inhibitor of cyclin-dependent kinases 4 and 6 (CDK4/6) in any setting and two to four prior chemotherapy regimens in the metastatic setting. Patients were randomly assigned to receive sacituzumab govitecan or treatment of physician’s choice (eribulin, gemcitabine, capecitabine, or vinorelbine). The primary endpoint was progression-free survival by independent review. Median follow-up was 10.2 months.
Membrane Trop-2 expression was determined on primary or metastatic archival tumor tissue by immunohistochemistry and expressed as a histochemical score (H-score; range, 0–300). Efficacy outcomes were assessed in groups of H-score < 100 and ≥ 100. The group with an H-score < 100 was further divided into subgroups of an H-score ≤ 10 and > 10 to < 100 to assess the activity of sacituzumab govitecan in patients with very low Trop-2 expression. Median time from tissue collection to study entry was 7.7 months.
Trop-2 expression was observed in about 95% of patients with evaluable samples, which included 88% of those given sacituzumab govitecan and 83% of those given treatment of physician’s choice. Within this group, the H-score was ≥ 100 in 58% of patients and < 100 in 42%. Demographics and baseline characteristics were generally consistent across H-score groups.
Consistent Benefit Across Trop-2 Levels
“There was no clear level of Trop-2 expression at which a better treatment effect for sacituzumab govitecan was observed,” Dr. Rugo reported.
For the subgroup with an H score < 100, median progression-free survival was 5.3 months with sacituzumab govitecan and 4.0 months with treatment of physician’s choice (HR = 0.77; 95% confidence interval [CI] = 0.54–1.09). For the subgroup with an H-score ≥ 100, these times were 6.4 months and 4.1 months, respectively (HR = 0.60; 95% CI = 0.44–0.81).
In the subgroup with an H-score ≤ 10, median progression-free survival was 5.5 months with sacituzumab govitecan and 4.3 months with treatment of physician’s choice (HR = 0.89; 95% CI = 0.51–1.57). For the subgroup with an H-score of > 10 to < 100, these times were 5.0 and 3.5 months, respectively (HR = 0.67; 95% CI = 0.424–1.07).
“The progression-free survival outcome favored sacituzumab govitecan across all Trop-2 H-score subgroups, including those with very low Trop-2 expression (H-score ≤ 10), though caution should be exercised in interpreting the data, given the small sample size,” Dr. Rugo said.
An overall survival benefit with sacituzumab govitecan over treatment of physician’s choice was observed in subgroups with a Trop-2 H-score < 100 and ≥ 100. For both subgroups, median overall survival was approximately 14 months with sacituzumab govitecan and 11 months with treatment of physician’s choice, representing risk reductions of 25% and 17%, respectively, she added. “Furthermore, an overall survival benefit was consistently observed across all Trop-2 H-score subgroups, including those with very low Trop-2 expression (H-score ≤ 10), though again, caution should be exercised in data interpretation” she added.
Responses are observed in all Trop-2 subgroups, including those with very low Trop-2 expression. The safety profile was consistent with previous reports and was not impacted by Trop-2 expression, she said.
DISCLOSURE: Dr. Rugo has served as a consultant or advisor to Puma Biotechnology, Napo, and Blueprint; has received travel support from Merck, AstraZeneca, GE Healthcare, and Gilead Sciences; and has received institutional research support from AstraZeneca, Ayala, Boehringer Ingelheim, Daiichi Sankyo, F. Hoffmann–La Roche, Genentech, Gilead Sciences, Lilly, MacroGenics, Merck, Napo, Novartis, OBI Pharma, Puma Biotechnology, Seattle Genetics, and Sermonic Pharmaceuticals.
1. Rugo HS, Bardia A, Marmé F, et al: Sacituzumab govitecan vs treatment of physician’s choice: Efficacy by Trop-2 expression in the TROPiCS-02 study of patients with HR+/HER2– metastatic breast cancer. 2022 San Antonio Breast Cancer Symposium. Abstract GS1-11. Presented December 6, 2022.
2. Rugo HS, Bardia A, Marmé F, et al: Sacituzumab govitecan in hormone receptor-positive/human epidermal growth factor receptor 2-negative metastatic breast cancer. J Clin Oncol 40:3365-3376, 2022.
3. Rugo HS, Bardia A, Marmé F, et al: Overall survival results from the phase III TROPiCS-02 study of sacituzumab govitecan vs treatment of physician’s choice in patients with HR+/HER2– metastatic breast cancer. ESMO Congress 2022. Abstract LBA76. Presented September 9, 2022.
Maryam B. Lustberg, MD, MPH
Maryam B. Lustberg, MD, MPH, Chief of Breast Medical Oncology at Yale Cancer Center, New Haven, shared her thoughts on TROPiCS-02 with The ASCO Post.
“The progression-free survival and overall survival results of the phase III TROPiCS-02 trial position sacituzumab ...