Palbociclib was not found to significantly improve invasive disease-free survival in patients with hormone receptor–positive, HER2-negative early breast cancer who had residual disease following neoadjuvant chemotherapy.
Palbociclib (Ibrance) was not found to significantly improve invasive disease-free survival (iDFS) in patients with hormone receptor (HR)–positive, HER2-negative early breast cancer who had residual disease following neoadjuvant chemotherapy, failing to meet the primary end point of the phase 3 PENELOPE-B trial (NCT01864746).1
Detailed data from the randomized, double-blind, placebo-controlled phase 3 trial anticipated to be presented at an upcoming medical meeting, according to The German Breast Group (GBG) and Pfizer Inc.
“Reducing the risk of disease recurrence in patients who have residual disease after neoadjuvant chemotherapy is a complex clinical challenge,” said Sibylle Loibl, MD, PhD, chair of the GBG.1 “This unique trial was made possible through the collaboration and support from all research partners involved. Despite this outcome, we believe that key learnings will emerge from the large number of biomarkers being analyzed from collected tumor tissue, which will help inform future breast cancer research.”
In the PENELOPE-B trial, investigators set out to compare 1 year of palbociclib in combination with at least 5 years of standard adjuvant endocrine therapy versus placebo plus at least 5 years of standard adjuvant endocrine therapy. A total of 1250 patients with HR-positive, HER2-negative early breast cancer who were at high risk of recurrence and had residual invasive disease following neoadjuvant chemotherapy were enrolled.
Participants on the trial scored 3 or higher on the clinical-pathologic stage – estrogen/grade, which is a validated risk assessment tool that incorporates clinical stage prior to neoadjuvant chemotherapy, pathological stage following neoadjuvant treatment, grading, and estrogen-receptor status.
To be eligible for participation, patients had to have histologically confirmed unilateral or bilateral primary invasive carcinoma of the breast, residual invasive disease following neoadjuvant treatment, acceptable surgical treatment, no clinical evidence of locoregional or distant relapse during or following preoperative chemotherapy, and an ECOG performance status of 0 or 1.2
If patients had unacceptable organ function prior to randomization, evidence of infection, uncontrolled electrolyte disorders, active inflammatory bowel disease or chronic diarrhea, short bowel syndrome, or any upper gastrointestinal surgery including gastric resection, they were not permitted for inclusion.
In the trial, patients on the experimental arm received palbociclib at a daily dose of 125 mg once daily, on days 1 to 21, followed by 7 days off, in a 28-day cycle for a total of 13 cycles. The control arm received palbociclib placebo for the same schedule.
The primary end point of the trial was iDFS for palbociclib versus placebo in patients with high CPS-EG score following neoadjuvant chemotherapy who were also receiving standard adjuvant endocrine therapy for their disease, while key secondary end points included iDFS excluding second non-breast cancers, distant disease-free survival, overall survival, safety, and patient-reported outcomes, among others.
“This is the first randomized phase 3 study to establish mature iDFS results for a CDK4/6 inhibitor as part of the adjuvant treatment for early breast cancer,” Chris Boshoff, MD, PhD, chief development officer of Oncology at Pfizer Global Product Development, added.1 “While we are disappointed with this result, we look forward to continuing to work with our research partners to understand subgroup data and how these could inform the development of our next-generation CDK inhibitors in early breast cancer.”
Previously, in June 2020, an independent data panel determined that the phase 3 PALLAS trial (NCT02513394), which was investigating the CDK4/6 inhibitor in patients with HR-positive, HER2-negative early breast cancer was not likely to lead to a statistically significant improvement in iDFS.3
Palbociclib was granted a full approval from the FDA in March 2017 for use in combination with letrozole in the frontline treatment of postmenopausal women with estrogen receptor–positive, HER2-negative metastatic breast cancer; it has also been approved for use in combination with fulvestrant in patients who progress on endocrine therapy. The CDK4/6 inhibitor is not yet indicated for patients with early breast cancer.