According to results from the PADMA trial, palbociclib plus endocrine therapy showed a statistically significant improvement in time to treatment-failure (TTF) and progression-free survival (PFS), with a trend toward improved overall survival (OS), when compared to mono-chemotherapy in the first line setting for patients with high-risk HR-positive, HER2-negative metastatic breast cancer. 

These results will be presented by Sibylle Loibl, MD, PhD, German Breast Group, Neu-Isenberg, Germany, at the 2024 San Antonio Breast Cancer Symposium. 

The prospective, open-label, multi-center, phase 3 PADMA trial enrolled 130 patients with previously untreated HR-positive, HER2-negative metastatic breast cancer who were indicated for chemotherapy. Patients were randomized to receive either 125 mg palbociclib on days 1 through 21 every 28 days in combination with endocrine therapy (palbociclib arm, n = 66) or mono-chemotherapy of the physician’s choice, with or without maintenance endocrine therapy (chemotherapy arm, n = 64). The primary end point of this trial was time to treatment-failure, defined as the time from randomization to discontinuation of treatment due to disease progression, treatment toxicity, patient’s preference, or death. Secondary end points included PFS, time to first subsequent treatment, OS, and safety.

There were a total of 120 patients who started treatment and were included in this analysis. The median follow-up duration was 36.8 months. In the palbociclib arm, 73.8% of patients experienced a TTF event compared to 93.2% in the chemotherapy arm. The median TTF was significantly longer in the palbociclib arm compared with the chemotherapy arm (17.2 months vs 6.1 months; hazard ratio [HR], 0.46; log-rank P = .0002).The leading cause of treatment failure was progression of disease, observed in 52.5% of patients in the palbociclib arm and 76.3% of patients in the chemotherapy arm. The median PFS was 18.7 months in the palbociclib arm vs 7.8 months in the chemotherapy arm (HR, 0.45; log-rank P = .0002). The median OS was numerically higher in the palbociclib group compared with the chemotherapy arm (46.1 months vs 36.8 months; HR, 0.81; log-rank P = .4630). 

Incidence of hematologic toxicity was significantly higher among patients in the palbociclib arm, and incidence of non-hematologic toxicities was comparable between arms. In the palbociclib arm, 6.5% of patients experienced a serious treatment-related adverse events compared to 10.3% in the chemotherapy arm. There was 1 treatment-related death, in the palbociclib arm.

Study authors concluded, “These results support existing international guidelines advocating the use of [endocrine therapy] plus CDK4/6 inhibitors as standard in [first-line] treatment” for patients with HR-positive, HER2-negative metastatic breast cancer.

Source:

Loibl S. Primary results of the randomised phase III trial comparing first-line ET plus palbociclib vs standard mono-chemotherapy in women with high risk HER2–/HR+ metastatic breast cancer and indication for chemotherapy – PADMA study. Presented at San Antonio Breast Cancer Symposium. Dec 10-13, 2024; San Antonio, TX. Abstract: SESS-3616