The Phase III PADMA trial has revealed that first-line endocrine therapy combined with palbociclib significantly extends the time to treatment failure in women with high-risk HER2-negative/HR-positive metastatic breast cancer, who are indicated for chemotherapy. The study, involving 130 patients, demonstrated a notable improvement with the endocrine-based treatment compared to standard mono-chemotherapy.
Key Findings from the PADMA Trial
Sibylle Loibl, MD, PhD, of the German Breast Group, presented the primary results of the PADMA trial, which compared endocrine therapy plus palbociclib against mono-chemotherapy in the first-line setting. The trial's primary endpoint, time to treatment failure, which included progression, death, treatment discontinuation due to toxicity, and patient preference, showed a significant increase from 7.2 months in the chemotherapy arm to approximately 17 months in the endocrine therapy plus palbociclib arm. This improvement was associated with a hazard ratio of 0.45, indicating a substantial benefit.
Progression-free survival (PFS), a key secondary endpoint, also favored the endocrine-based treatment. Patients on mono-chemotherapy experienced a PFS of about seven months, while those on the palbociclib combination saw a considerably longer PFS. Overall survival (OS) also tended to be longer in the endocrine-based treatment arm, with an approximately 10-month difference, although this did not reach statistical significance in this analysis.
Implications for Clinical Practice
According to Dr. Loibl, these results, combined with previous data, suggest that chemotherapy should no longer be considered a standard first-line treatment for patients with hormone receptor-positive, HER2-negative metastatic breast cancer. "The standard of care is and remains an endocrine-based treatment for now with a CDK 4/6 inhibitor," she stated. She also noted the potential for triplet combinations in patients with PI3K kinase mutations, further supporting the shift towards endocrine-based strategies.
Safety and Tolerability
Regarding toxicity, the study found no significant differences in non-hematologic toxicities between the treatment arms. As expected, palbociclib was associated with a higher rate of hematologic toxicity. Conversely, capecitabine, a common chemotherapy agent used in the mono-chemotherapy arm, led to more frequent occurrences of diarrhea and hand-foot syndrome.
Study Design
The PADMA trial was a randomized phase III study designed to evaluate the superiority of endocrine therapy plus palbociclib over mono-chemotherapy in patients with hormone receptor-positive HER2-negative metastatic breast cancer. The primary endpoint was time to treatment failure, with secondary endpoints including progression-free survival and overall survival. The patient population included women with high-risk disease who were candidates for chemotherapy.
