The PADMA phase 3 trial demonstrated that combining palbociclib with endocrine therapy significantly outperformed standard chemotherapy in treating high-risk hormone receptor–positive/HER2-negative metastatic breast cancer.
A phase 3 clinical trial, known as PADMA, has paved a promising new path for treating high-risk hormone receptor (HR)-positive/HER2-negative metastatic breast cancer (mBC), in which primary results were presented at the 2024 San Antonio Breast Cancer Symposium. The study directly compared the efficacy of 2 treatment approaches: a combination of palbociclib, a CDK4/6 inhibitor, with endocrine therapy (ET), versus standard single-agent chemotherapy (CT) with or without maintenance ET. The results revealed a significant advantage for the combination therapy, offering a beacon of hope for patients facing this challenging diagnosis.
PADMA is a prospective, randomized, open-label, multicenter phase 3 trial and the first trial to compare standard single-agent CT followed by maintenance ET with a CDK4/6 inhibitor plus ET as first-line therapy in patients with high-risk mBC. Previously untreated patients were randomized to receive either palbociclib 125 mg on days 1 to 21 every 28 days in combination with ET, or mono-CT of physician’s choice with or without following maintenance ET. The primary endpoint was time to treatment failure (TTF). Secondary endpoints included progression-free survival (PFS), time to first subsequent treatment, overall survival (OS), and safety.
The PADMA trial enrolled 130 participants across 28 German sites, of which 120 patients started treatment and were included in the analysis (61 palbociclib + ET arm, 59 CT-based arm). The study found that the combination of palbociclib and ET resulted in a significantly longer median TTF compared with CT alone—17.2 months versus 6.1 months, respectively (P=<.001). This remarkable difference translates to a substantial delay in disease progression and a longer period of time during which patients can benefit from their initial treatment.
Further solidifying the superiority of the combination therapy, the trial also assessed PFS, another critical indicator of treatment effectiveness. Again, the palbociclib/ET group outperformed the CT group, demonstrating a median PFS of 18.7 months compared with 7.8 months for those receiving CT alone (P=<.001). Although the trial observed a trend toward improved OS with palbociclib/ET, this difference did not reach statistical significance. While the trend is encouraging, further research and longer follow-up are needed to definitively determine whether the combination therapy translates into an OS advantage.
It is important to note that the palbociclib/ET regimen did come with a higher incidence of hematologic toxicity, primarily affecting blood cell counts. However, nonhematologic adverse events were comparable between the 2 treatment groups. The potential benefits of improved TTF and PFS must be carefully weighed against the risk of hematologic adverse events, which can often be managed with supportive care measures.
The PADMA trial’s robust findings provide support for international guidelines recommending ET combined with CDK4/6 inhibitors as the standard first-line treatment for patients with high-risk, HR-positive/HER2-negative mBC.
Loibl S, et al. Primary results of the randomized 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. December 10, 2024; San Antonio, TX. Abstract SESS-3616.