In a Chinese single-institution phase II trial (FUTURE-SUPER) reported in The Lancet Oncology, Fan et al found that molecular subtype–based therapy produced promising results in the first-line treatment of metastatic or recurrent triple-negative breast cancer.
Study Details
In the open-label trial, 139 women at Fudan University Shanghai Cancer Center were randomly assigned between July 2020 and October 2022 to control treatment with nab-paclitaxel at 100 mg/m² on days 1, 8, and 15 of 28-day cycles (n = 70) or subtype-based treatment (n = 69).
Subtype-based treatment consisted of 28-day cycles of:
- Pyrotinib at 400 mg daily for the luminal androgen receptor (LAR) HER2-mutant subtype
- Everolimus 10 mg daily for the LAR PI3K/AKT-mutant and mesenchymal-like (MES) PI3K/AKT-mutant subtypes
- Camrelizumab at 200 mg on days 1 and 15 and famitinib at 20 mg daily for the immunomodulatory subtype
- Bevacizumab at 10 mg/kg on days 1 and 15 for the basal-like immune-suppressed/MES PI3K/AKT-wild-type subtype.
The primary endpoint was investigator-assessed progression-free survival in the pooled subtype–based treatment group vs the control group in the intention-to-treat population.
Key Findings
At data cutoff in May 2023, median follow-up was 22.5 months (interquartile range = 15.2–29.0 months).
Median progression-free survival was 11.3 months (95% confidence interval [CI] = 8.6–15.2 months) in the pooled subtyping–based group vs 5.8 months (95% CI = 4.0–6.7 months) in the control group (hazard ratio [HR] = 0.44, 95% CI = 0.30–0.65, P < .0001). Improvement in progression-free survival was consistent across all subgroups in the pooled subtyping–based group.
Among 118 patients with baseline measurable disease, objective response was achieved in 48 (80.0%) of 60 in the pooled subtyping–based group vs 26 (44.8%) of 58 in the control group (odds ratio = 4.92, 95% CI = 2.17–11.15). Median duration of response was 12.0 months vs 4.2 months (HR = 0.44, 95% CI = 0.26–0.78).
At time of analysis, death had occurred in 26% vs 27% of patients (HR = 0.82, 95% CI = 0.38–1.56).
The most common grade 3 or 4 treatment-related adverse events in the subtyping-based group vs the control group were neutropenia (30% vs 23%), anemia (7% vs 0%), and increased alanine aminotransferase (6% vs 1%). Treatment-related serious adverse events occurred in 10% vs 0% of patients. No treatment-related deaths were reported.
The investigators concluded, “These findings highlight the potential clinical benefits of using molecular subtype–based treatment optimization in patients with triple-negative breast cancer, suggesting a path for further clinical investigation. Phase III randomized clinical trials assessing the efficacy of subtyping-based regimens are now underway.”
Zhi-Ming Shao, MD, and Yi-Zhou Jiang, MD, of Fudan University Shanghai Cancer Center, are the corresponding authors for The Lancet Oncology article.
Disclosure: The study was funded by the National Natural Science Foundation of China, Natural Science Foundation of Shanghai, Jiangsu Hengrui Pharmaceuticals, and others. For full disclosures of the study authors, visit thelancet.com.
