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Sacituzumab govitecan shows promise for advanced triple-negative breast cancer
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SAN ANTONIO — Sacituzumab govitecan induced significant clinical activity as monotherapy in the third-line setting of patients with relapsed or refractory metastatic triple-negative breast cancer, according to results of a phase1/phase 2 basket trial presented at the San Antonio Breast Cancer Symposium.
“Metastatic triple-negative breast cancer, in general, is aggressive and has a poor prognosis. It tends to affect young women and African American women,” Aditya Bardia, MBBS, MPH, assistant professor of medicine at Harvard Medical School and attending physician of medical oncology at Massachusetts General Hospital, told HemOnc Today. “Responses to standard chemotherapy agents, particularly beyond first line, are not very high, at about 10% to 15%. We need agents that would improve response rates and PFS.”
Sacituzumab govitecan (IMMU-132, Immunomedics) is an antibody drug conjugate comprised of SN-38 — the active metabolite of irinotecan, a topoisomerase inhibitor — conjugated to an anti-Trop-2 humanized monoclonal antibody. Trop-2 is highly expressed on most epithelial cancers, including triple-negative breast cancer.
Bardia and colleagues evaluated sacituzumab govitecan in a basket trial of patients with advanced epithelial cancers.
“Sacituzumab govitecan was evaluated in triple-negative breast cancer first because it was a clinically unmet need,” Bardia said.
As HemOnc Today previously reported, preliminary results from the metastatic triple-negative breast cancer cohort (n = 69) — published earlier this year — showed an objective response rate of 30%. Based on these promising data, the FDA granted sacituzumab govitecan breakthrough therapy designation and researchers expanded enrollment of this cohort in a more defined population of patients in the third-line setting.
The updated analysis included data from 110 patients (women, n = 109; median age, 55 years; range, 31-81) — including 53 patients from the preliminary analysis with at least two prior regimens — who received third-line sacituzumab govitecan 10 mg/kg on days 1 and 8 of a 21-day cycle.
As of the June 30, 2017, data cutoff, 71 patients had died, 23 continued in long-term follow-up and 16 remained on treatment.
Patients received a median of 14.5 doses (range, 1-88).
Local radiologist assessment showed an ORR of 34% (n = 37), which included three complete responses and 34 partial responses. The clinical benefit rate — which also included stable disease for at least 6 months — was 45%. Median duration of response was 7.6 months (95% CI, 4.8-11.3) by local assessment and 9.1 month (95% CI, 4.1-14.3) by independent review.
Median time to response was 2 months.
“However, this response ranged from 1.5 to 13.4 months, so there were some responses with later cycles,” Bardia said during his presentation.
Median PFS was 5.5 months (95% CI, 4.8-6.6) and included 10% of patients (n = 11) who experienced long-term PFS ranging from 12 to 30+ months.
Median OS was 12.7 months (95% CI, 10.8-13.6).
Researchers conducted exploratory analyses looking at patient subgroups, such as age, onset of metastatic disease, visceral involvement at study entry and the number of prior regimens for metastatic disease.
“The bottom line was there was no difference in response to sacituzumab by looking at [these factors],” Bardia said.
These subgroups included an analysis based on Trop-2 expression. Immunohistochemical (IHC) testing defined 57 patients as having moderate or strong Trop-2 expression, five patients as having weak expression and 48 patients as having no Trop-2 expression.
Researchers reported ORRs of 0% in the weak expression group, 40% in the strong expression group and 29% in the no expression group.
“The majority of patients had Trop-2 expression of IHC 2+ or 3+,” Bardia told HemOnc Today. “So, the number of patients who had expression of 0 to 1 was very low. This was a single-arm study of only 110 patients, and we need a much larger study to really look at this Trop-2 question.”
No treatment-related deaths occurred, and only two patients discontinued treatment due to toxicity. Researchers observed no antidrug antibodies.
Common grade 3 or worse toxicities included neutropenia (39%), leukopenia (14%) and anemia (10%). Researchers noted incidence of febrile neutropenia was low, at 7%.
The ASCENT phase 3 trial is recruiting patients to evaluate sacituzumab govitecan in metastatic triple-negative breast cancer. The drug’s company also has announced it will file for regulatory approval of sacituzumab govitecan next year based on these and earlier data.
“We saw a response rate of 31% by independent review and 34% by local assessment,” Bardia said. “That is almost double compared with what one would anticipate with standard chemotherapy based on historical data. This was not a randomized trial but, in general, it suggests that this was an active drug, and that’s why there is excitement about this.” – by Alexandra Todak
Reference:
Bardia A, et al. Abstract GS1-07. Presented at: San Antonio Breast Cancer Symposium; Dec. 5-9, 2017; San Antonio.
Disclosures: Immunomedics funded this study. Please see the abstract for a list of all authors’ relevant financial disclosures.