Fuzuloparib ± apatinib improves PFS in BRCA-mutated metastatic breast cancer

Treatment with fuzuloparib, with or without apatinib, significantly improved progression-free survival (PFS) in patients with HER2– metastatic breast cancer (mBC) harbouring germline BRCA1/2 (gBRCA1/2) mutations compared with standard chemotherapy, according to results of a phase III study presented at ESMO 2024.

The study met its primary endpoint, demonstrating a significant improvement in PFS, as assessed by Blinded Independent Central Review (BICR), with the combination of fuzuloparib and apatinib or fuzuloparib monotherapy vs the physician’s choice of standard chemotherapy, said lead author Professor Huiping Li from the Department of Breast Oncology at Peking University Cancer Hospital and Institute in Beijing, China.

This phase III, open-label, multicentre, part two study included 203 patients with HER2– mBC and  gBRCA1/2 mutations who were randomized 1:1:1 to receive fuzuloparib 100 mg BID + apatinib 500 mg QD (n=70), fuzuloparib 150 mg BID (n=67), or standard chemotherapy* (n=66). Those who experienced disease progression on standard chemotherapy were allowed to switch to fuzuloparib monotherapy.

As per the BICR assessment, the median PFS was significantly longer in patients treated with fuzuloparib + apatinib and fuzuloparib alone than those treated with standard chemotherapy (11 and 6.7, respectively vs 3 months; hazard ratios [HRs], 0.27; p<0.0001 and 0.27; p=0.0004), meeting the superiority of the combination regimen and monotherapy over standard chemotherapy. [ESMO 2024, abstract VP2-2024]

Notably, the fuzuloparib + apatinib arm also had a significantly better PFS when compared with the fuzuloparib alone arm (HR, 0.60; p=0.0079).

In addition, an overall survival trend favouring fuzuloparib + apatinib and fuzuloparib alone (median 29.2 and 31.5 months, respectively; HRs, 0.58 and 0.61) was observed over standard chemotherapy (median 21.5 months), “despite a crossover rate of 39.4 percent from standard chemotherapy to fuzuloparib,” Li noted.

With regard to tumour response based on BICR, the objective response rates were numerically higher in the fuzuloparib + apatinib (67.3 percent) and fuzuloparib alone arms (43.6 percent) than the standard chemotherapy arm (23.3 percent).

The disease control rate was also higher for patients on fuzuloparib + apatinib (87.1 percent) and fuzuloparib alone (80.6 percent) compared to those receiving standard chemotherapy (47 percent), with a median duration of response of 9.8, 7.6, and 3.9 months for the respective cohorts.

Safety

Grade ≥3 treatment-related adverse events (TRAEs) occurred in 51.4 percent of patients on the combination regimen, 49.3 percent on fuzuloparib monotherapy, and 40.7 percent on standard chemotherapy.

Of note, fewer serious TRAEs were observed in the combination arm (12.9 percent) compared with fuzuloparib alone (17.9 percent) and standard chemotherapy arms (13.9 percent). However, a higher rate of TRAEs led to the discontinuation of treatment with the combination regimen compared with standard chemotherapy (7.1 percent vs 3.4 percent).

“The profile and severity of toxicity were consistent with previous reports of fuzuloparib and apatinib,” said Li.

“Overall, the present study met both its primary and key secondary objectives [in terms of achieving] superiority in BICR-assessed PFS … with fuzuloparib + apatinib or fuzuloparib alone compared with standard chemotherapy,” said Li.

“Our findings support the use of fuzuloparib + apatinib or fuzuloparib alone for HER2– mBC patients with a gBRCA mutation,” she added.