Sacituzumab Govitecan Improves PFS in HR+/HER2- Metastatic Breast Cancer

Sacituzumab govitecan-hziy (Trodelvy) improved median progression-free survival (PFS) compared with physician’s choice of chemotherapy in patients with HER2-low breast cancer with an immunohistochemistry (IHC) score of 0, 1, 2 and who have a negative in-situ hybridization (ISH) test.¹

These data come from a post hoc subgroup analysis from the phase 3 TROPiCS-02 study (NCT03901339) which is evaluating sacituzumab govitecan-hziy vs physicians’ choice of chemotherapy in patients with hormone receptor–positive (HR+)/HER2- metastatic breast cancer who progressed on endocrine-based therapies and at least 2 chemotherapies.

Findings showed that the median PFS of patients with HER2-low breast cancer in the sacituzumab govitecan arm (n = 149) was 6.4 months vs 4.2 months in the standard of care arm (n =134; HR, 0.58; 95% CI, 0.42-0.79). For the IHC0 group, patients given sacituzumab govitecan (n = 101) had a median PFS of 5.0 months vs 3.4 when given physicians choice of chemotherapy (n = 116; HR, 0.72; 95% CI, 0.51-1.00). In the intention-to-treat population, the median PFS was 5.5 months (95% CI, 4.2-7.0) with sacituzumab govitecan vs 4.0 months (95% CI, 3.1-4.4) with investigator’s choice chemotherapy (HR, 0.66; 95% CI, 0.53-0.83; P < .0003).

“These data demonstrate Trodelvy’s efficacy across HER2-low and IHC0 status in pre-treated metastatic breast cancer patients in the TROPiCS-02 trial,” said Peter Schmid, professor of Cancer Medicine, center lead, at Center of Experimental Cancer Medicine, director of Barts Breast Cancer Center, in the press release. “Once patients have developed resistance to endocrine-based therapies, their prognosis is extremely poor. The results highlight the potential for Trodelvy as a treatment option for people living with pre-treated HR+/HER2- metastatic breast cancer, regardless of their HER2-negative status.”

The phase 3 TROPiCS-02 study enrolled patients with hormone receptor–positive, HER2-negative metastatic breast cancer who were refractory to or relapsed after at least 2 prior systemic chemotherapy regimens for metastatic disease, including at least 1 prior anticancer hormonal treatment and at least 1 CDK4/6 inhibitor administered in the metastatic setting.²

Enrollment in the trial was open to patients aged 18 years and older who received no more than 4 prior lines of chemotherapy prior to enrollment, measurable disease per RECIST 1.1 criteria, documented disease progression after their most recent therapy, and adequate bone marrow, renal, and hepatic function.

Patients were randomly assigned 1:1 to receive sacituzumab govitecan at 10 mg/kg via intravenous infusion on days 1 and 8 of a 21-day cycle or investigator’s choice chemotherapy until progression or unacceptable toxicity.

The primary end point of the trial was PFS with secondary end points including overall survival (OS), duration of response, clinical benefit rate, quality of life, and safety.

According to data presented at the 2022 American Society of Clinical Oncology Annual Meeting, treatment with sacituzumab govitecan demonstrated a statistically significant and clinically meaningful reduction in the risk of disease progression of 34% in this patient population with endocrine therapy resistance vs with treatment with standard chemotherapy.

While the overall survival (OS) data were not mature at the time of the primary analysis, investigators noted a numeric trend toward improvement with the antibody-drug conjugate vs standard care.

Between the 2 arms, baseline characteristics were well balanced with the median age in the investigative arm at 57 years (range, 29-86) vs 55 years (range, 27-78) in the control arm.³ The majority of the patients had liver metastases at baseline (84% and 87%, respectively), had an ECOG performance status of 1 (57% and 54%), and had received a prior CDK4/6 inhibitor within 12 months (59% and 61%). For those who received sacituzumab govitecan and those who received chemotherapy, the median number of prior lines of chemotherapy in the metastatic setting was 3 (range, 0-8 and range, 1-5).

Regarding safety, no new toxicity signals were observed with sacituzumab govitecan and those that were shown were manageable based on observations in prior studies. The most common adverse events were diarrhea and neutropenia. Among the 6 deaths reported in the sacituzumab govitecan arm, 1 was related to treatment.

Sacituzumab govitecan is currently not approved by any regulatory agency for the treatment of HR+/HER2- metastatic breast cancer as its safety and efficacy have not been established for this indication. However, a supplemental biologics license application has been submitted to the FDA based on data from TROPiCS-02.

Expanded findings will be presented during a mini-oral session at the European Society for Medical Oncology (ESMO) Congress 2022 on September 10.

“These results show Trodelvy improved progression-free survival regardless of HER2 status in this pre-treated patient population and reinforce the strength of clinical activity in a population where need is highest,” said Bill Grossman, MD, PhD, senior vice resident, Therapeutic Area Head, Gilead Oncology. “Trodelvy is already transforming the standard of care in second-line metastatic triple-negative breast cancer, and we’re excited about its potential in other breast cancers where there is significant need for new treatment options.”

References:

1. New TROPiCS-02 data in HR+/HER2- metastatic breast cancer patients demonstrates progression-free survival benefit of trodelvy® regardless of their HER2 status. News release. Gilead Sciences, Inc. September 4, 2022. Accessed September 6, 2022. https://bit.ly/3qdhDyL

2. Study of sacituzumab govitecan-hziy versus treatment of physician’s choice in participants with HR+/HER2- metastatic breast cancer (TROPiCS-02). ClinicalTrials.gov. Updated May 5, 2022. Accessed September 6, 2022. https://clinicaltrials.gov/ct2/show/NCT03901339

3. Rugo HS, Bardia A, Marmé F, et al. Primary results from TROPiCS-02: a randomized phase 3 study of sacituzumab govitecan (SG) versus treatment of physician’s choice (TPC) in patients (Pts) with hormone receptor–positive/HER2-negative (HR+/HER2-) advanced breast cancer. J Clin Oncol. 2022;40(suppl 17):LBA1001. doi:10.1200/JCO.2022.40.17_suppl.LBA1001