The latest analysis of the TROPiCS-02 breast cancer trial shows that 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 (Abstract GS1-11).
“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.
Hope S. Rugo, MD, FASCO
High Trop-2 expression is observed in patients with breast cancer regardless of subtype. Sacituzumab govitecan is a Trop-2–directed antibody‑drug conjugate approved for pretreated patients with metastatic triple-negative breast cancer. It has subsequently been evaluated in hormone receptor–positive patients in the phase III TROPiCS-02 study, where it significantly improved progression-free survival (hazard ratio [HR] = 0.66, P < .0003) and overall survival (HR = 0.79, P = .02) as compared to 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.
Study Details
The 543 patients enrolled in the trial 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 CDK4/6 inhibitor 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 H-score < 100 and ≥ 100 groups. The H-score < 100 group was further divided into H-score ≤ 10 and > 10 to < 100 subgroups 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 the sacituzumab govitecan cohort and 83% of the treatment of physician’s choice cohort. Within this group, 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.
A benefit in progression-free and overall survival was observed for sacituzumab govitecan vs treatment of physician’s choice across the two main Trop-2 groups (H-score < 100 and ≥ 100). For the < 100 subgroup, 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 ≥ 100 subgroup, these rates were 6.4 months and 4.1 months, respectively (HR = 0.60, 95% CI = 0.44–0.81).
In the H-score ≤ 10 subgroup, 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 > 10 to < 100 subgroup, these rates 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 Trop-2 H-scores of < 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 given the small sample size,” she added.
Responses were 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, Dr. Rugo concluded.
Disclosure: Dr. Rugo has consulted for or provided advisory support to Puma, NAPO, and Blueprint; has received travel support from Merck, AstraZeneca, GE Healthcare, and Gilead; and has received institutional research support from numerous entities.
