The phase 3 PALLAS trial exploring palbociclib (Ibrance) in patients with HR-positive, HER2-negative early breast cancer is unlikely to demonstrate a statistically significant improvement in the study’s primary end point of invasive disease-free survival.
Chris Boshoff, MD, PhD, senior vice president and head of Immuno-Oncology, Early Development, Translational Oncology, Pfizer Global Product Development
Chris Boshoff, MD, PhD
An independent data panel determined that the phase 3 PALLAS trial exploring palbociclib (Ibrance) in patients with HR-positive, HER2-negative early breast cancer is unlikely to demonstrate a statistically significant improvement in the study’s primary end point of invasive disease-free survival (iDFS), according to Pfizer, Inc., the manufacturer of the CDK4/6 inhibitor.1
The assessment came from a preplanned efficacy and futility analysis. No new safety signals emerged with palbociclib in the trial. The specific data from the trial is not yet available.
“We are disappointed in this outcome. Breast cancer is a leading cause of death around the world and delaying or preventing the development of metastatic disease is a significant unmet need. PALLAS is a large study with many subgroups and we are actively collaborating to determine if there are patients who may benefit from adjuvant treatment with the palbociclib combination," Chris Boshoff, MD, PhD, chief development officer, Oncology, Pfizer Global Product Development, stated in a press release. “Since its initial approval in 2015, Ibrance has helped change the treatment landscape for people with HR-positive, HER2-negative metastatic breast cancer. We are grateful to all patients, health care providers and our academic partners who have devoted so much to make this important study possible.”
The international, multicenter, open-label phase 3 PALLAS study randomized patients with HR-positive/HER2-negative early breast cancer to palbociclib combined with standard adjuvant endocrine therapy, or standard adjuvant endocrine therapy alone. The purpose of the trial was to determine whether adding 2 years of palbociclib to standard adjuvant endocrine therapy would improve outcomes in this setting. The primary end point was iDFS. Patients on the trial were treated at more than 400 clinical sites in 21 countries.
Palbociclib is approved by the FDA for the treatment of adult patients with HR-positive, HER2-negative advanced or metastatic breast cancer in combination with an aromatase inhibitor as initial endocrine based therapy in postmenopausal women or in men; or with fulvestrant in patients with disease progression following endocrine therapy.
Multiple randomized trials and clinical analyses have demonstrated the benefit of palbociclib in various settings in patients with HR-positive/HER2-negative breast cancer. One such study was the pivotal, double-blind phase 3 PALOMA-2 study, in which postmenopausal women with ER-positive/HER2-negative advanced breast cancer were randomized in a 2:1 ratio to frontline treatment with palbociclib plus letrozole or placebo plus letrozole. The study, which led to the full FDA approval of the palbociclib combination in this setting, showed a median progression-free survival at 38 months’ follow-up of 27.6 months with the palbociclib combination versus 14.5 months with letrozole alone (HR, 0.56; P <.0001).2
Palbociclib is not, however, approved by the FDA for the treatment of patients with early breast cancer, and researchers have been seeking to demonstrate a benefit with the use of the CDK4/6 inhibitor in this setting. For example, the ongoing phase 3 PENELOPE-B study (NCT01864746) is evaluating the addition of palbociclib to standard endocrine treatment in patients with HR-positive, HER2-normal primary breast cancer with a high risk of relapse after neoadjuvant chemotherapy.