Medical Information

Sacituzumab govitecan resulted in a statistically significant improvement in progression-free survival vs physician’s choice of chemotherapy in patients with hormone receptor–positive, HER2-negative metastatic breast cancer who previously received endocrine therapy, CDK4/6 inhibitors, and 2 to 4 lines of chemotherapy, meeting the primary end point of the phase 3 TROPiCS-02 trial.

Sacituzumab govitecan-hziy (Trodelvy) resulted in a statistically significant improvement in progression-free survival (PFS) vs physician’s choice of chemotherapy in patients with hormone receptor–positive, HER2-negative metastatic breast cancer who previously received endocrine therapy, CDK4/6 inhibitors, and 2 to 4 lines of chemotherapy, meeting the primary end point of the phase 3 TROPiCS-02 trial (NCT03901339).

The open-label, multicenter trial targeted a 30% reduction in the risk of disease progression or death, and the data proved to be consistent with those that had been reported in the phase 1/2 IMMU-132-01 trial (NCT01631552) that was done in a subgroup of patients with this disease.

Moreover, findings from the first interim analysis of the key secondary end point of overall survival (OS) in TROPiCS-02 showcased a trend in improvement with the antibody-drug conjugate (ADC) over chemotherapy. Participants will be followed for a subsequent OS analysis, according to a press release issued by Gilead Sciences, Inc.

No new safety signals were reported with the agent in this population.

“[Sacituzumab govitecan] demonstrated consistent activity in this difficult-to-treat patient population,” Merdad Parsey, MD, PhD, chief medical officer of Gilead Sciences, stated in the press release. “We are evaluating the data and will explore potential pathways with regulatory authorities to bring [sacituzumab govitecan] to this group of patients. As we work to expand the patient benefit of [the drug] beyond its current indications for second-line metastatic triple-negative breast cancer [TNBC] and accelerated approval in second-line metastatic bladder cancer, we are pursuing studies across multiple tumor types and earlier lines of therapy.”

A novel ADC, sacituzumab govitecan is comprised of an anti–Trop-2 antibody coupled to SN-38, the active metabolite of irinotecan, through a unique hydrolysable linker. Previously, data from the IMMU-132-01 basket trial showed that among 108 heavily pretreated patients with TNBC who received the ADC at 10 mg/kg on days 1 and 8 of 21-day cycles, the drug produced an objective response rate (ORR) of 33% at a data cutoff of December 1, 2017.

The median duration of response (DOR) with the agent was 7.7 months (95% CI, 4.9-10.8) per local assessment. Moreover, the median PFS was 5.5 months (95% CI, 4.1-6.3) and the median overall survival (OS) was 13.0 months (95% CI, 11.2-13.7).

TROPiCS-02 enrolled patients with metastatic or locally advanced inoperable hormone receptor–positive, HER2-negative metastatic breast cancer who had experienced disease progression on, or after, at least 1 endocrine therapy, taxane, and CDK4/6 inhibitor. Patients must have received at least 2, but no more than 4, lines of chemotherapy in the metastatic setting, and they also needed to have measurable disease per RECIST v1.1 criteria. Patients also needed to have an ECOG performance status of 0 or 1, and acceptable bone marrow, renal, and hepatic function.

If they previously received Topo 1 inhibitors, had a history of significant cardiovascular disease, or a clinically significant ECG abnormality, they were excluded. Other exclusion criteria included having active central nervous system metastases, unless stable for at least 4 weeks, having active infections that needs intravenous systemic treatment or active chronic inflammatory bowel disease with prior bowel obstruction, or having additional concurrent medical or psychiatric conditions.

Investigators of the trial planned to enroll 400 patients who would be randomized 1:1 to receive the ADC at a dose of 10 mg/kg on days 1 and 8, every 21 days, or physician’s choice of chemotherapy, which could have included capecitabine, vinorelbine, gemcitabine, or eribulin. Treatment was administered until progressive disease, intolerable toxicity, withdrawn consent or withdrawal per investigator decision.

Patients were stratified based on visceral metastases (presence vs absence), duration of endocrine treatment in the metastatic setting (6 months or longer vs not), and the number of previous lines of chemotherapy received (2 vs 3 vs 4).

The primary end points of the trial include PFS and ORR per local investigator review and RECIST v1.1 criteria, and key secondary end points include OS, clinical benefit rate, DOR, and safety. Biomarkers and quality of life serve as exploratory end points.

Detailed data from the trial will be shared at an upcoming medical meeting, according to Gilead Sciences.

“Patients with advanced breast cancer may eventually develop endocrine resistance, then resistance to a limited set of sequential chemotherapy options,” Hope Rugo, MD, professor of medicine and director of Breast Oncology and Clinical Trials Education at the University of California San Francisco Comprehensive Cancer Center, added in the press release. “These data show the potential for [sacituzumab govitecan] to address an important unmet need for patients with hormone receptor–positive, HER2-negative metastatic breast cancer who have been heavily pretreated.”

References

1.Phase 3 TROPiCS-02 study met the primary endpoint of progression-free survival in late-line HR+/HER2- metastatic breast cancer. News release. Gilead Sciences, Inc.; March 7, 2022. Accessed March 7, 2022. https://bit.ly/374lAQ1

2.Rugo HS, Bardia A, Tolaney SM, et al. TROPiCS-02: a phase III study investigating sacituzumab govitecan in the treatment of HR+/HER2- metastatic breast cancer. Future Oncol. 2020;16(12):705-715. doi:10.2217/fon-2020-0163

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