Sacituzumab Govitecan: SABCS 2022 Sara Tolaney vs Chemo TROPiCS-02

Sacituzumab Govitecan: SABCS 2022 Sara Tolaney vs Chemo TROPiCS-02

By Sara Tolaney, MD

What were the patient-reported outcomes from the TROPiCS-02 trial? So this year at San Antonio, we saw data from TROPiCS-02. This was a randomized phase 3 study that compared Sacituzumab Govitecan (SG), which is a novel antibody drug conjugate, to standard of care chemotherapy in patients with metastatic hormone receptor positive breast cancer.

We’d seen results from this trial previously, initially at ASCO, we saw data regarding progression-free survival (PFS), demonstrating that Sacituzumab Govitecan (SG) led to an improvement in progression-free survival compared to chemotherapy in patients with breast cancer. And then at ESMO, we actually saw the overall survival data suggesting that there was a significant improvement in overall survival (OS) going from about 11 to a little over 14 months. So a little over a 3 month improvement in OS (overall survival). And so at the San Antonio Breast Cancer Symposium (SABCS), what we saw were data regarding Trop-2 expression and outcomes in patients with breast cancer. One question is whether using an antibody drug conjugates, such as Sacituzumab Govitecan (SG), that targets Trop-2 wood levels of Trop-2 results in differential activity of Sacituzumab Govitecan (SG). One would think that if you had a higher Trop-2 level, you may have greater efficacy from Sacituzumab Govitecan (SG) since you may get greater payload delivery to those cancer cells. And so in this particular analysis, they looked at Trop-2 expression from archival tumor samples from patients enrolled in this trial, they looked at Trop-2 levels, and then they looked at efficacy, and what they found was that patients with breast cancer who had high Trop-2 expression compared to those who had lower Trop-2 expression all seemed to derive greater benefit from Sacituzumab Govitecan (SG) compared to standard of care chemotherapy. So whether you had a very high Trope-2 or even a very low Trop-2, Sacituzumab Govitecan (SG) always outperformed standard chemotherapy.

So I think these data are important because one of the questions we’ve had clinically is, does one actually need to test for Trop-2 to figure. If someone’s going to have a very significant benefit to Sacituzumab Govitecan (SG), these data suggest that you don’t actually need to test for Trop-2 levels because even people with very low Trop-2 levels still did better with Sacituzumab Govitecan (SG) compared to chemotherapy.

So I think this is important data for us to know and really suggests no need for Trop-2 expression testing at this time. I do think there are limitations, though, because, as you know, this was done off of archival tumor tissue, and we don’t really have data looking at the most current Trop-2 level and its association with outcome.

And so that will be important for us to learn. There are other clinical trials where this data could be ascertained. There was a preoperative trial called NeoSTAR looking at preoperative Sacituzumab Govitecan (SG). This was triple-negative breast cancer. But I think it will be really interesting to look at baseline Trop-2 expression and how it may correlate, for example, with the achievement of pCR (pathologic complete response). So I think much more is to come, but it is very important to learn that at this time, there is no need for testing for Trop-2 to select breast cancer patients for use of Sacituzumab Govitecan (SG).

I think the data that we’re seeing from TROPiCS-02 is actually very consistent with previous data that we’ve seen since we know in the ASCENT trial, which had lead led to the actual initial registration of Sacituzumab Govitecan (SG) and breast cancer. That study had compared Sacituzumab Govitecan (SG) to chemotherapy in patients with metastatic triple-negative disease (breast cancer) and shown improvements in PFS (progression-free survival) and OS (overall survival), but it had also looked at Trop-2 expression and its association with outcomes and actually had very similar findings that there was benefit for Sacituzumab Govitecan (SG) relative to chemotherapy, irrespective of Trop-2 expression. So I think the data from TROPiCS-02 are very much in line with our previous presentations of data with regards to Trop-2 express.

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5 Key Stats for Sacituzumab Govitecan Used in Breast Cancer

• Sacituzumab Govitecan markedly increased progression-free survival (PFS; median 4.8 vs 1.7 mo) 

• The overall survival (OS; median 11.8 vs 6.9 mo) vs single-agent chemotherapy of physician’s choice (TPC) in the second line or greater (2L+) mTNBC setting.

• Pts with mTNBC who received ≥2 prior systemic therapies (at least 1 for metastatic breast cancer) were randomized to receive SG (10 mg/kg IV on d 1 and 8, every 21 d) or TPC (capecitabine, eribulin, vinorelbine, or gemcitabine).

• The HRQoL was assessed at baseline (BL), before each cycle, and at end of treatment (Tx) using the EORTC QLQ-C30. The HRQoL analysis included all pts with valid HRQoL assessments at BL and at ≥1 post-BL visit. Linear mixed-effect models for repeated measures were calculated using on-Tx data for cycles 2 to 6 (where n was ≥25 in both arms) to estimate differences in overall least-square (LS) mean changes from BL between Tx arms.

• HRQoL analysis included 419 (236 SG; 183 TPC) pts (median age, 54 y; median prior regimens, 4; brain metastases present, 11%). Mean QLQ-C30 sub-scale scores at BL were similar between Tx arms. SG showed significantly and meaningfully greater improvement than TPC (Table) in global health status (GHS, 0.7 vs -3.4), physical (1.3 vs -4.4) and emotional functioning (3.3 vs. -0.5), and lower symptomatic impact of fatigue (2.0 vs 7.1), pain (-8.9 vs -1.9), dyspnea (-3.8 vs 4.0), and insomnia (-4.7 vs 0.3). Of all symptoms, only diarrhea was significantly and meaningfully worse with SG (14.1 vs. -1.3).

Is sacituzumab govitecan chemotherapy?

Irinotecan, a chemotherapeutic drug, is attached to an antibody to form sacituzumab govitecan. Antibodies are immune system proteins that bind to foreign substances in the body to prevent damage. Sacituzumab govitecan binds to cancer cells and eliminates them.

Abstract Tropics-2 Sacituzumab Govitecan (SG)

There is a clinical need that is not being fulfilled for patients with HR+/HER2- metastatic breast cancer (MBC) whose illness has progressed in spite of receiving standard treatment. It has been shown that the transmembrane calcium signal transducer Trop-2, which is highly expressed in MBC, plays a role in the development and disease progression of malignancies. Sacituzumab govitecan (SG) is a new antibody-drug combination that consists of a Trop-2 antibody connected to SN-38, the active metabolite of irinotecan, using an unique hydrolyzable linker. This linker is what makes Sacituzumab govitecan (SG) a novel antibody-drug combination. SG shown promising activity in highly pretreated solid tumors, such as HR+/HER2- MBC, during a Phase I/II IMMU-132-01 basket study. In this article, we discuss the registrational Phase III TROPiCS-02 research that compared physician-selected treatment to SG in HR+/HER2- MBC (breast cancer) patients. NCT03901339 is the number of trial that has been registered.

About Gilead Sciences, Inc.

Gilead Sciences, Inc. is a biopharmaceutical company that has spent over three decades seeking and achieving medical advancements in an effort to make the world a better place for everyone. HIV, viral hepatitis, and cancer are among the life-threatening conditions that the company is committed to preventing and treating with innovative medications. Gilead operates in approximately 35 countries worldwide, with company headquarters located in Foster City, California.

The ASCENT study was sponsored by Gilead Sciences, Inc. Gilead Sciences, Inc. (Nasdaq: GILD) today reported the findings of the Phase 3 ASCENT trial of Trodelvy® (sacituzumab govitecan-hziy) in patients with relapsed or refractory metastatic triple-negative breast cancer (TNBC) who had undergone at least one prior systemic therapy for metastatic breast cancer illness. Trodelvy improved median progression-free survival versus physicians’ choice of chemotherapy (4.8 vs. 1.7 months; HR: 0.41; p0.0001) and extended median overall survival (OS) by nearly five months (11.8 vs. 6.9 months; HR: 0.51) in a follow-up analysis from the final database lock in the population intended to be treated. The two-year OS rate in the Trodelvy (sacituzumab govitecan) arm was 20.5% (95 percent confidence interval: 15.4-26.1), compared to 5.5% (95 percent confidence interval: 2.8-9.4) in the chemotherapy arm. In addition to chemotherapy, Trodelvy (sacituzumab govitecan) has demonstrated clinically significant improvements in health-related quality of life (HRQL). Abstract #1071 was presented at the American Society of Clinical Oncology (ASCO) Annual Meeting in 2022. They were consistent with The New England Journal of Medicine’s previously published final analysis.

Consistent with previous data, Trodelvy (sacituzumab govitecan) demonstrated larger clinically relevant improvements in all five primary HRQL domains than chemotherapy. Measuring the impact of symptom load is particularly pertinent in this case, as metastatic TNBC is typically associated with a substantial decline in quality of life, especially when patients are treated to repeated cycles of intensive treatment. Compared to chemotherapy, Trodelvy (sacituzumab govitecan) improved global health status by -5.8 versus -9.4, physical functioning by -4.6 versus -13.5, role functioning by -8.4 versus -18.8, fatigue by 5.1 versus 14.0, and pain by 2.8 versus 6.8.

Sara M. Tolaney, MD, MPH – About The Author, Credentials, and Affiliations

Dr. Sara Tolaney attended Princeton University for her undergraduate degree in 1998 and the University of California, San Francisco, for her medical degree in 2002. After she finished medical school at Johns Hopkins, she went to the Dana-Farber Cancer Institute for fellowships in hematology and medical oncology. She earned her MPH from the Harvard School of Public Health in 2007. In 2008, she began working as a medical oncologist and clinical investigator at the Breast Oncology Center at Brigham and Women’s Hospital and the Dana-Farber Cancer Institute. These schools can be found in the city of Boston, MA. Her research is mostly concerned with finding new ways to treat breast cancer.

Reference

1. NIH National Cancer Institute – Clinical Trials Using Sacituzumab Govitecan. NIH Clinical Trials Information, 2022.

2. NIH National Cancer Institute – Sacituzumab Govitecan Earns Full Approval for Triple-Negative Breast Cancer. NIH Cancer Currents Blog, May 12, 2021.

3. NIH National Cancer Institute – TROPiCS-02: A Phase III study investigating sacituzumab govitecan in the treatment of HR+/HER2- metastatic breast cancer. NIH Clinical Trials Information, 2022

4. Breast Cancer Now The Research & Care Charity –
   Sacituzumab govitecan (Trodelvy) – Breast Cancer Now The Research & Care Charity Targeted (Biological) Therapy, February 2022.

5. The New England Journal of Medicine – Sacituzumab Govitecan in Metastatic Triple-Negative Breast Cancer, The New England Journal of Medicine Original Article, April 22, 2021