First-line endocrine therapy (ET) plus palbociclib (palb/ET) performs better than mono-chemotherapy in improving time to treatment failure (TTF) and progression-free survival (PFS) in women with hormone receptor-positive (HR+), HER2-negative metastatic breast cancer (mBC), as shown by the results of the phase III PADMA trial.

In addition, a trend for an improved overall survival (OS) is also observed in patients who received palbociclib plus ET.

“The PADMA trial in high-risk hormone receptor?positive, HER2-negative mBC met its primary endpoint and demonstrated a statistically significant and clinically meaningful improvement in TTF, which is a very patient-centric endpoint, as well as PFS,” said lead author Dr Sibylle Loibl, chair of the German Breast Group in Germany. [https://www.oncologynewscentral.com/breast-cancer/palbociclib-plus-endocrine-therapy-beats-chemo-in-metastatic-breast-cancer]

Loibl and her team randomly allocated 130 patients, who were enrolled at 28 German sites between April 2018 and December 2023 and previously untreated for HR+/HER- mBC with an indication for chemotherapy, to receive either palbociclib 125 mg on days 1?21 q28 plus ET (n=66) or mono-chemotherapy (n=64) of physician’s choice with or without following maintenance ET.

Participants received treatment until disease progression, unacceptable toxicity, consent withdrawal, or modification to the initial treatment plan. TTF, the primary endpoint, was defined as time from randomization to treatment discontinuation due to disease progression, treatment toxicity, patient’s preference or death.

Among trial participants, 120 (median age 62 years) initiated treatment and were included in the final analysis. Of these, 12 (10 percent) were pre-/perimenopausal, 90 (75 percent) had metastases in two or more organ systems, 52 (43.3 percent) had symptomatic disease, 10 (8.3 percent) were endocrine-resistant at enrolment. [SABCS 2024, abstract LB1-03]

Among patients treated with chemotherapy, 40 (69.0 percent) received capecitabine, 17 (29.3 percent) paclitaxel, and one (1.7 percent) vinorelbine. Thirteen (22. 4percent) out of 58 patients receiving chemotherapy switched to maintenance ET.

Disease progression

A TTF event occurred in 45 patients in the palb/ET arm and 55 in the mono-chemotherapy arm (73.8 percent vs 93.2 percent) over a median follow-up of 36.8 months. The median TTF was significantly longer with palb/ET (17.2 vs 6.1 months; hazard ratio [HR], 0.46, 80 percent confidence interval [CI], 0.35?0.60; p=0.0002), with progression as the main cause (52.5 percent vs 76.3 percent).

PFS was also significantly longer with palb/ET than mono-chemotherapy (median, 18.7 vs 7.8 months; HR, 0.45, 95 percent CI, 0.29?0.70; p=0.0002), as was time to first subsequent treatment (median, 19.9 vs 8.0 months; HR, 0.52, 95 percent CI, 0.34?0.80; p=0.0028).

Notably, patients who received palb/ET demonstrated a numerically longer OS than those treated with mono-chemotherapy (median, 46.1 vs 36.8 months; HR, 0.81, 95 percent CI, 0.46?1.43; p=0.4630).

However, the palb/ET arm showed significantly higher hematologic toxicity relative to the mono-chemotherapy arm (any grade: 96.8 percent vs 70.7 percent; p<0.001; high grade: 56.5 percent vs 10.3 percent; p<0.001), whereas nonhematologic toxicity did not significantly differ between groups.

In addition, four patients (6.5 percent) in the palb/ET arm and six (10.3 percent) in the mono-chemotherapy arm experienced serious treatment-related adverse events, with one treatment-related death recorded in the palb/ET group.

“These results support existing international guidelines advocating the use of ET plus CDK4/6 inhibitors as standard in [the] first-line treatment of HR+/HER2- mBC,” Liobl said.