Clinical Relevance

  • Patient-reported outcomes of ASCENT-03 clinical trial show that sacituzumab govitecan-hziy (Trodelvy) has fewer adverse events compared to standard of care chemotherapy for people with previously untreated, locally advanced inoperable or metastatic TNBC. 
  • Previously reported data showed that sacituzumab govitecan helps people with newly diagnosed TNBC live longer without cancer progression. 
  • PROs confirm sacituzumab govitecan as a possible first-line treatment for people with advanced TNBC who are ineligible for immune checkpoint inhibitors and have few other treatment options. 

More evidence is supporting sacituzumab govitecan-hziy (Trodelvy) as a first-line treatment for patients with previously untreated advanced triple-negative breast cancer (TNBC) who are ineligible for immunotherapy. Patient-reported outcomes (PROs) from the ASCENT-03 clinical trial confirm that the antibody-drug conjugate is a safe and effective treatment, showing improved progression-free survival (PFS) and less frequent dose reductions or treatment discontinuations compared to chemotherapy.

Sacituzumab govitecan is already approved for advanced TNBC as a third-line treatment. With these PROs, oncologists are hopeful that the indication will be expanded to a first-line therapy.

“[Sacituzumab govitecan] works better and longer than chemotherapy, so it makes sense to position the treatment that is most likely to produce a response or that will have the longest duration of response,” said Dr. Kevin Punie of University Hospitals Leuven, Gasthuisberg, Belgium. “This is a very aggressive disease and there are data that show up to 50% of patients with metastatic triple-negative breast cancer in real-world settings do not make it to a second line of treatment. This treatment improves PFS and has an overall positive impact on quality of life upfront.”

What is the ASCENT-03 clinical trial?

The phase 3 ASCENT-03 (NCT05382299) study is an ongoing international, randomized clinical trial comparing the antibody-drug conjugate sacituzumab govitecan with standard of care chemotherapy for previously untreated, locally advanced and unresectable or metastatic TNBC. 

TNBC is an aggressive and difficult-to-treat subtype of breast cancer, accounting for between 10% and 20% of all breast cancer diagnoses in the United States. Recent treatment advances with PD-1 and PD-L1 inhibitors have improved outcomes for some people with TNBC, but some TNBC tumors do not express PD-1/PD-L1. For these patients, there are limited treatment options.

Previously reported data from the ASCENT-03 clinical trial showed improvements in median progression-free survival for those treated with sacituzumab govitecan (9.7 months) compared to chemotherapy (6.9 months). These new data compare the safety profile of the antibody-drug conjugate with chemotherapy.

What did the patient-reported outcomes of the ASCENT-03 clinical trial show?

To compare outcomes between the two groups, researchers used exposure-adjusted incidence rate or EAIR. This measurement takes the number of patients experiencing an adverse event (AE) divided by the total patient-year of exposure or PYE, which is the amount of time patients were at risk of the specific outcome.

Almost all of the participants experienced some treatment-related AEs, with 99% of those treated with sacituzumab govitecan and 97% of those treated with chemotherapy reporting AEs. In the sacituzumab govitecan arm, 66% experienced grade 3 or higher AEs compared to 62% in the chemotherapy arm. 

The most common AEs in the sacituzumab govitecan arm were:

  • Neutropenia (67%, 2.48 EAIR)
  • Diarrhea (54%, 1.42 EAIR)
  • Fatigue (47%, 1.15 EAIR)
  • Anemia (39%, 0.77 EAIR)

In the chemotherapy arm, the most common AEs were:

  • Neutropenia (57%, 2.01 EAIR)
  • Anemia (50%, 1.51 EAIR)
  • Fatigue (47%, 1.24 EAIR)
  • Thrombocytopenia (28%, 0.63 EAIR)

Both diarrhea and neutropenia were more common in the sacituzumab govitecan arm. Most of the diarrhea cases were grade 1 or 2 and were treated with antidiarrheals, and there were 15 patients who needed a dose reduction due to diarrhea in the sacituzumab govitecan arm. There were no treatment discontinuations caused by diarrhea. 

There were 54 patients in both groups who needed a dose reduction due to neutropenia, and 1 patient in the sacituzumab govitecan arm and 3 patients in the chemo arm discontinued treatment due to neutropenia. When prophylactic G-CSF was given for neutropenia, it was less frequent and less severe.

There were 7 deaths in the sacituzumab govitecan arm, with 6 caused by treatment-related infections. Five of those were secondary to neutropenia in patients who were at a high risk of febrile neutropenia and did not receive prophylaxis with G-CSF.

The duration of the diarrhea and neutropenia was comparable between the two treatment arms. 

These data show that sacituzumab govitecan provides better outcomes for progression-free survival while maintaining a better quality of life during treatment. 

What’s next for sacituzumab govitecan?

Research is ongoing to test this antibody-drug conjugate as a first-line treatment for TNBC, but oncologists are hopeful that the indication will be expanded for sacituzumab govitecan for those patients who are ineligible for immune checkpoint inhibitors. However, it may be some time before it is available widely in the clinic for this indication. 

“At the moment, this drug is not yet approved in this setting, so it will take some time before this drug is widely implemented as a first-line treatment for untreated advanced TNBC. But these data do support the approval, and will probably help get this new treatment to patients faster,” said Dr. Punie.