Sacituzumab govitecan improves survival in pretreated triple-negative breast cancer
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Sacituzumab govitecan significantly improved PFS and OS compared with single-agent chemotherapy among patients with pretreated metastatic triple-negative breast cancer, according to findings presented during ESMO Virtual Congress 2020.
The primary results of the randomized, phase 3, confirmatory ASCENT study also showed sacituzumab govitecan (Trodelvy, Immunomedics) — an antibody-drug conjugate consisting of an anti–Trop-2 antibody coupled to the active metabolite of irinotecan, SN-38 — was well-tolerated and had a safety profile consistent with that previously observed.
“Sacituzumab govitecan is a first-in-class Trop-2-directed antibody-drug conjugate that is unique from others and has several unique properties,” Aditya Bardia, MD, MPH, assistant professor in the department of medicine at Harvard Medical School and attending physician in the department of medical oncology at Massachusetts General Hospital, said during his presentation. “It was granted accelerated approval by the FDA for metastatic triple-negative breast cancer and fast-track designation in metastatic urothelial cancer.”
That accelerated approval was based on previously reported data showing a 33% overall response rate and a median PFS of 5.5 months.
To confirm those results, Bardia and colleagues randomly assigned 468 patients with relapsed or refractory metastatic triple-negative breast cancer 1:1 to 10 mg/kg IV sacituzumab govitecan on days 1 and 8 of each 21-day cycle (n = 235; median age, 54 years; range, 29-82; 99% women; 80% white) or treatment with physician’s choice of either capecitabine, eribulin (Halaven, Eisai), vinorelbine or gemcitabine (n = 233; median age, 53 years; range, 27-81; 100% women; 78% white) until disease progression or unacceptable toxicity.
All patients were previously treated with two or more prior chemotherapies (median, 4).
PFS as measured by central review per RECIST v1.1 among patients without brain metastases served as the primary endpoint. OS, ORR by RECIST v1.1 and safety served as dual secondary endpoints.
“Earlier this year, the ASCENT trial was halted early due to compelling evidence of efficacy per unanimous data and safety monitoring committee recommendation,” Bardia said. “Additional results, including biomarker [analyses] and [data in patients with] brain metastases, will be reported during a future meeting.”
Results showed treatment with sacituzumab govitecan significantly improved median PFS (5.6 months vs. 1.7 months; HR = 0.41; P < .0001) and median OS (12.1 months vs. 6.7 months; HR = 0.48; 95% CI, 38-59).
Similar results were observed for investigator-assessed PFS (HR = 0.35) as well as for the overall patient population (n = 529), which included patients with brain metastases (HR = 0.42), Bardia added.
“The PFS benefit of sacituzumab govitecan vs. chemotherapy was consistent across all prespecified subgroups, including age, race, prior chemotherapy, prior checkpoint inhibitor use and liver metastases,” he said.
Moreover, ORR was 35% with sacituzumab govitecan compared with only 5% with single-agent chemotherapy (P < .0001).
Researchers reported no treatment-related deaths with sacituzumab govitecan. The most common grade 3 treatment-related adverse events with that treatment included neutropenia (51%), diarrhea (10.5%), anemia (8%) and febrile neutropenia (6%), whereas the most common of these in the chemotherapy group were neutropenia (33%), diarrhea (< 1%), anemia (5%) and febrile neutropenia (2%).
“This is the first phase 3 study to demonstrate a significant improvement in efficacy with sacituzumab govitecan, which reduced the risk for progression by 59%. Improvements were observed across all prespecified subgroups,” Bardia said. “The clinical benefit here confirms the use of sacituzumab govitecan as a standard therapy for patients with pretreated metastatic triple-negative breast cancer.
“Ongoing studies are evaluating the use of sacituzumab govitecan in earlier lines of therapy, including the neoadjuvant setting in combination with other targeted agents as well as hormone receptor-positive metastatic breast cancer, such as in the phase 3 TROPiCS-02 study,” he added.
Perspective
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Fatima Cardoso, MD
In the metastatic setting, and particularly for triple-negative breast cancer where the median survival is quite low and where each line of treatment has a short duration, the primary endpoint should have been OS. It was also not clear to me why the trial was stopped early as there was no benefit in stopping the trial. It is very important to not stop trials early.
I want to highlight that the median number of prior lines was four up until 17 lines, which is quite remarkable.
The PFS and OS results are quite good. In terms of toxicity, there is a substantial percentage of diarrhea and nausea, but there is a small number of patients who stopped treatment due to toxicity. In my opinion, we should now add sacituzumab govitecan as a new treatment option for patients treated with two or more lines of prior therapy.
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Bardia A, et al. Abstract LBA17. Presented at: European Society for Medical Oncology Virtual Congress 2020; Sept. 19-21, 2020.
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