By Mary Ellen Schneider
The addition of 1 year of the CDK4/6 inhibitor palbociclib to endocrine therapy did not improve invasive disease-free survival (IDFS) in hormone receptor (HR)-positive, HER2-negative primary breast cancer in patients at high risk for relapse following neoadjuvant chemotherapy, according to results from the PENELOPE-B trial.
The study, which were presented at the 2020 San Antonio Breast Cancer Symposium, failed to meet its primary endpoint of IDFS (Abstract GS1-02).
“To date, the results of the PENELOPE-B study do not support the addition of 1 year of palbociclib to endocrine therapy. It could be that the treatment duration with 1 year is too short, but we don’t know that,” said Sibylle Loibl, MD, PhD, chair of the German Breast Group, who presented the results. “Long term follow up from all adjuvant CDK4/6 studies should continue and must be awaited.”
The phase 3 trial randomized 1,250 women with HR-positive, HER2-negative primary breast cancer to receive neoadjuvant chemotherapy and surgery, plus or minus radiotherapy, with either 1 year of palbociclib and endocrine therapy or placebo and endocrine therapy. The median age of study participants was 49 years.
At a median follow up of 42.8 months, there were 152 IDFS events in the group of patients receiving palbociclib and endocrine therapy, compared with 156 events in the group receiving placebo plus endocrine therapy. The stratified hazard ratio (HR) was 0.93 (95% CI, 0.74-1.17; P=0.525).
The results were consistent across subgroups, regardless of age, risk status, and Ki-67 status. “No group could be identified with a higher benefit from Palbociclib,” Dr. Loibl said.
Nearly three-quarters of the IDFS events were distant recurrences, with 116 in the palbociclib group and 111 in the placebo group. Another 16% of events were invasive locoregional recurrences, which were also similar between the two groups. Contralateral breast cancer, second primary invasive non-breast cancer, and death without a previous event were less common.
An interim analysis on overall survival also failed to show a benefit for palbociclib. At 42.8 months of follow-up, there were 62 events in the palbociclib group, compared with 69 events in the placebo group (stratified HR 0.87; 95% CI 0.61-1.22; P=0.420).
Compliance with treatment was somewhat lower with palbociclib than with placebo. In total, 80.5% of patients receiving palbociclib completed treatment, compared with 84.5% of patients receiving placebo. However, 88.6% of patients in the palbociclib group received at least seven cycles of treatment versus 90.3% of patients in the placebo group. The relative total dose intensity was 82% with palbociclib versus 99% with placebo.
“Although the compliance was lower in the palbociclib arm, it was still satisfactory and the relative total dose intensity was over 80% with palbociclib,” Dr. Loibl said.
Ruth O’Regan, MD, of the University of Wisconsin, Madison, who was a discussant during the PENELOPE-B presentation, said the curves showing the declining disease-free survival benefit over time versus placebo raised the question of whether the trial is just treating occult metastatic disease.
“These curves kind of mirror what we might see in the first-line metastatic setting,” Dr. O’Regan said.
Another possibility is that PENELOPE-B might have been positive if the duration of treatment had been longer, Dr. O’Regan said.