December 11, 2020
2 min read
Loibl S, et al. Abstract GS1-02. Presented at: San Antonio Breast Cancer Symposium (virtual meeting); Dec. 8-11, 2020.
Pfizer provided financial and drug support for this study. Loibl reports grants from AbbVie, Amgen, AstraZeneca, Bristol Myers Squibb, Celgene, Daiichi Sankyo, Eirgenix, Eli Lilly, Immunomedics, Novartis, Pfizer, prIME Oncology/Medscape, Puma Biotechnology, Merck, Roche, Samsung, Seattle Genetics, Teva and Vifor Pharma, and personal fees from Chugai. Please see the abstract for all other researchers’ relevant financial disclosures.
The addition of 1 year of palbociclib to endocrine therapy failed to improve invasive DFS among women with hormone receptor-positive, HER2-negative high-risk breast cancer, according to results of the phase 3 PENELOPE-B trial.
“Patients without pathologic complete response have an inferior prognosis compared with those with pathologic complete response, and this is also true for patients with hormone receptor-positive, HER2-negative primary breast cancer,” Sibylle Loibl, MD, PhD, CEO and chair of the German Breast Group and associate professor at University of Frankfurt, said during her presentation at the virtual San Antonio Breast Cancer Symposium. “The CDK4/6 inhibitor palbociclib [Ibrance, Pfizer] in combination with endocrine therapy prolongs PFS and OS in metastatic breast cancer. The aim of the PENELOPE-B trial was to evaluate whether palbociclib would prevent relapses [in the post-neoadjuvant setting.]”
The analysis included data of 1,250 women (median age, 49.7 years; range, 19-79) with hormone receptor-positive, HER2-negative primary breast cancer who did not achieve a pathologic complete response after taxane-based neoadjuvant chemotherapy. Women were deemed at high risk for relapse if they had a score of 3 or higher on the clinical pathologic stage-estrogen/grade staging system (CPS-EG), which included 59.4% of the women, or a CPS-EG score of 2 and pathologic node-positive disease (40.6%).
In total, 96.8% of women had residual disease in the breast, 50.4% had two to three positive nodes, and 25.5% had a Ki-67 percentage score greater than 15%.
After the women underwent surgery with or without radiotherapy, the researchers randomly assigned them 1:1 to receive 125 mg palbociclib daily on days 1 through 21 of 13 28-day cycles or placebo for 1 year. All women also received endocrine therapy at the discretion of their clinician, with 49.8% in each group receiving tamoxifen or an aromatase inhibitor.
Invasive DFS (iDFS) served as the study’s primary endpoint. Secondary endpoints included distant DFS, locoregional recurrence-free interval, OS, safety and compliance.
A total of 1,244 women started therapy (palbociclib, n = 628; placebo, n = 616), and 82.5% (palbociclib, 80.5%; placebo, 84.5%) completed all 13 treatment cycles. Relative dose intensity was 82% for palbociclib and 99% for placebo, which, although suggesting lower compliance for palbociclib, still was satisfactory because it was over 80%, Loibl said.
About 18% of women discontinued therapy, with more women in the palbociclib group discontinuing due to adverse events (5.2% vs. 0.8%).
Median follow-up was 42.8 months.
At 2 years, the iDFS rates favored the palbociclib group (88.3% vs. 84%). But, by 4 years, iDFS rates were 73% in the palbociclib group and 72.4% in the placebo group, which did not represent a significant improvement (stratified HR = 0.93; 95% CI, 0.74-1.17). Researchers did not find any group of women who benefited from palbociclib on subgroup analysis, Loibl said.
Distant recurrences represented 74% of iDFS events and invasive locoregional recurrences accounted for 16%.
An interim OS analysis showed 4-year OS rates of 90.4% in the palbociclib group and 87.3% in the placebo group (stratified HR = 0.87; 95% CI, 0.61-1.22).
Researchers observed no new safety signals related to treatment with palbociclib. Significantly more women treated with palbociclib experienced any-grade (99.2% vs. 79.1%) and grade 3 to grade 4 (73.1% vs. 1.3%; P < .001 for both) hematologic adverse events.
“We can say that this is the first study showing mature iDFS results for a CDK4/6 inhibitor as part of post-neoadjuvant or adjuvant therapy,” Loibl said. “To date, the results of PENELOPE-B do not support the addition of 1 year of palbociclib to endocrine therapy. It could be that the treatment duration of 1 year is too short, but we don’t know that. Long-term follow-up from other adjuvant CDK4/6 inhibitor studies should continue and are awaited.”