Phase 3 PENELOPE-B Trial Fails to Meet Meet Primary End Point for HR+, HER2- Early Breast Cancer

The phase 3 PENELOPE-B trial did not meet its primary end point of improved invasive disease-free survival (DFS) in women with hormone receptor (HR)-positive HER2-negative early breast cancer who have residual invasive disease after completing neoadjuvant chemotherapy, according to the German Breast Group and Pfizer, which are collaborating on the trial.

Notably though, no unexpected safety signals were observed.

“Reducing the risk of disease recurrence in patients who have residual disease after neoadjuvant chemotherapy is a complex clinical challenge,” Sibylle Loibl, MD, PhD, chair of the German Breast Group, said in a press release. “This unique trial was made possible through the collaboration and support from all the 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.”

The randomized, double-blind, placebo-controlled, phase 3 PENELOPE-B trial is comparing 1 year of palbociclib (Ibrance) plus at least 5 years of standard adjuvant endocrine therapy to placebo plus at least 5 years of standard adjuvant endocrine therapy. Overall, 1250 women with HR-positive, HER2-negative early breast cancer at high risk of recurrence who have residual invasive disease after completing neoadjuvant chemotherapy were enrolled in the trial.

Patients included in the study scored 3 or higher (or 2 if there were lymph node metastases at the time of surgery) on the clinical-pathologic stage – estrogen/grade (CPS-EG). The CPS-EG is a validated risk assessment tool which combines clinical stage before neoadjuvant treatment, pathological stage after neoadjuvant treatment, grading, and estrogen-receptor status.

“This is the first randomized phase 3 study to establish mature [invasive] DFS results for a CDK4/6 inhibitor as part of the adjuvant treatment for early breast cancer. 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,” Chris Boshoff, MD, PhD, chief development officer of Oncology at Pfizer Global Product Development, said in the release.

“We are proud of the transformative impact [palbociclib] has had on the treatment of HR[-positive], HER2[-negative] metastatic breast cancer - a vastly different treatment setting than early breast cancer,” Boshoff continued. “Our commitment to the metastatic patient community is as strong as ever as we continue to generate new data, including the most extensive body of real-world evidence for a CDK 4/6 inhibitor.”

Over 190 clinical sites across 12 countries globally participated in PENELOPE-B. The study opened in November 2013 and closed recruitment on December 31, 2017.

Detailed findings from the trial will be presented at an upcoming medical congress.

Reference:

PENELOPE-B TRIAL OF IBRANCE® (PALBOCICLIB) IN EARLY BREAST CANCER DID NOT MEET PRIMARY ENDPOINT [news release]. Neu-isenburg, Germany & Frankfurt, Germany & New York. Published October 9, 2020. Accessed October 9, 2020. https://www.pfizer.com/news/press-release/press-release-detail/penelope-b-trial-ibrancer-palbociclib-early-breast-cancer