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Triple-negative breast cancer (TNBC) patients saw a significant survival benefit when treated with third-line sacituzumab govitecan (Trodelvy) rather than chemotherapy, phase III findings from the ASCENT trial showed.

The trial met it's primary endpoint, improving median progression-free survival (PFS) in patients without brain metastases and whose disease progressed on at least two earlier lines of therapy, from 1.7 months with physician's choice of chemotherapy to 5.6 months with sacituzumab govitecan (HR 0.41, 95% CI 0.32-0.52, P<0.0001), reported Aditya Bardia, MD, MPH, of Harvard Medical School in Boston.

And median overall survival (OS) improved from 6.7 months with single-agent chemotherapy to 12.1 months with the antibody-drug conjugate (HR 0.48, 95% CI 0.38-0.59, P<0.0001), he said during a presentation at the 2020 European Society for Medical Oncology (ESMO) virtual congress.

Sacituzumab govitecan also induced significantly more responses, at 35% compared to 5% with chemotherapy, including complete responses in 4% and 1%, respectively. Patients on sacituzumab govitecan also had a higher clinical benefit rate (response plus stable disease), at 45% versus 9% in the control arm. At data cutoff, 15 patients remained on sacituzumab govitecan versus none in the control arm.

"The clinical benefit here confirms the use of sacituzumab govitecan as a standard therapy for patients with pretreated metastatic triple-negative breast cancer," Bardia said.

Sacituzumab govitecan is a monoclonal antibody directed against trophoblast cell-surface antigen (Trop)-2, which is linked to a topoisomerase inhibitor chemotherapeutic agent. Trop-2 is highly expressed in breast cancer.

FDA recently granted accelerated approval to the agent as a third-line treatment for metastatic TNBC based on single-arm findings that demonstrated responses in a third of patients, with some lasting beyond 12 months. Continued approval is contingent on results from confirmatory trials, such as ASCENT.

ASCENT "is the first phase III study to demonstrate a significant improvement in efficacy with a first-in-class Trop-2-directed antibody-drug conjugate compared to standard chemotherapy in patients with previously treated metastatic triple-negative breast cancer," said Bardia.

The most common adverse events (AEs) of any grade included neutropenia in 63%, diarrhea in 59%, nausea in 57%, alopecia in 46%, fatigue in 45%, and anemia in 34%. Common grade 3/4 AEs included neutropenia in 63%, leukopenia in 11%, diarrhea in 10%, anemia in 8%, and febrile neutropenia in 6%.

In the investigational arm, 4.7% of patients stopped treatment due to AEs, while 5.4% stopped for toxicity in the chemotherapy arm. There were no treatment-related deaths with the study drug versus one in the chemotherapy arm (sepsis).

ASCENT randomized 529 TNBC patients at 88 sites in seven countries 1:1 to either intravenous sacituzumab govitecan (10 mg/kg on days 1 and 8 every 3 weeks) or physician's choice of chemotherapy (eribulin [n=139], vinorelbine [n=52], gemcitabine [n=38], or capecitabine [n=33]), with treatment until disease progression or unacceptable toxicity.

Patients were required to have received at least two prior chemotherapies for advanced disease. Patients with brain metastases -- a group with poor prognosis -- could enroll on the trial but were limited to 15% of the population to avoid potential confounding. Most participants were women (99%) with a median age 54, and 79% were white. All had received prior taxane chemotherapy and about a third in each arm had previously received a checkpoint inhibitor.

The primary endpoint was PFS in patients without brain metastases (n=468) on blinded central review, and the results were consistent across all prespecified subgroups, including age, race, region, prior chemotherapy, liver involvement, and prior checkpoint inhibitor use. Secondary endpoints included PFS of the full population (HR 0.43, 95% CI 0.35-0.54, P<0.0001), as well as OS, levels of response, and safety.

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