The sponsor is set to apply for TGA approval for the new indication, which led to longer progression-free survival and fewer treatment discontinuations at trial than comparative therapy.
Combining an antibody–drug conjugate with an immune checkpoint inhibitor led to a 35% lower risk of disease progression or death than chemotherapy with immunotherapy, a new phase 3 trial has found.
Sacituzumab govitecan (Trodelvy) plus pembrolizumab (Keytruda) outperformed chemotherapy plus pembrolizumab in survival, adverse effects causing discontinuation, and rates and duration of response among patients with previously untreated, PD-L1–positive, advanced triple-negative breast cancer
Participants had locally advanced unresectable or metastatic triple-negative breast cancer, PD-L1–positive tumours and no previous therapy for advanced disease. The open-label trial recruited patients from 186 sites across 28 countries.
The 443 patients were randomly assigned to either the combination therapy or the control group. The combination therapy was sacituzumab govitecan 10mg per kilogram of body weight on days one and eight plus pembrolizumab at a 200mg fixed dose on day one of a 21-day cycle.
The chemotherapy group received the same dose and frequency of pembrolizumab alongside chemotherapy (paclitaxel or gemcitabine plus carboplatin at standard dosing schedules). The median duration of treatment was 8.9 months for the combination therapy group and 6.2 months for the chemotherapy group.
Median progression-free survival was 11.2 months in the treatment group, compared with 7.8 months in the control group – a 35% lower risk of disease progression or death (hazard ratio 0.65).
The proportion of patients achieving an objective response was also higher with the combination therapy, at 60% compared with 53% for chemotherapy plus pembrolizumab.
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Among patients who responded to treatment, responses lasted longer in the sacituzumab govitecan group, with a median response duration of 16.5 months compared with 9.2 months in the chemotherapy group.
Overall survival data were immature, and a reliable median survival could not be calculated.
Adverse events occurred in 99.5% of patients in both groups. However, far fewer patients in the combination therapy group discontinued treatment because of adverse effects (12% vs 31%). Grade 3 or higher events occurred at similar rates across the two groups (71% and 70%, respectively) and events leading to death occurred in 3% of the patients in each group.
The most common adverse events in the treatment group were diarrhea (70% of patients), nausea (68%) and neutropenia (63%), compared to neutropenia (59%), fatigue (56%) and anaemia (51%) in the control group.
The most common grade 3 or higher events in the combination group were neutropenia (43%), diarrhea (10%) and fatigue (8%), and neutropenia (45%), anaemia (16%) and thrombocytopenia (14%) in the chemotherapy group.
While both drugs in the treatment arm are widely used in Australia, sacituzumab govitecan – sponsored by Gilead Sciences – is not currently an approved first-line treatment and PBS funding only applies after at least two previous therapies. Pembrolizumab is PBS-listed for this patient group, but not in combination with sacituzumab govitecan.
“Gilead is submitting for TGA approval this month for Trodelvy as a first-line treatment for PD-L1-positive metastatic TNBC,” a spokesperson told Oncology Republic.
“ASCENT04 demonstrated that Trodelvy (sacituzumab govitecan), in combination with pembrolizumab, significantly improved progression free survival compared with pembrolizumab plus chemotherapy in patients with previously untreated, PDL1–positive metastatic triple negative breast cancer, with a safety profile consistent with the known profiles of each medicine.”
