Palbociclib Expected to Miss Its Mark in HR+, HER2– Breast Cancer

Preplanned interim analysis results from the phase 3 PALLAS trial, as reported by an independent Data Monitoring Committee, hint that palbociclib (Ibrance) as treatment of patients with stage II or III hormone receptor (HR)–positive, HER2-negative breast cancer will not achieve statistical significance for the primary end point of invasive disease-free survival (iDFS), Pfizer, Inc. announced in a press release.

Despite the strong possibility of negative results, long-term follow-up in PALLAS will continue as planned.

“We are disappointed [with] 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," said Chris Boshoff, MD, PhD, chief development officer, Oncology, Pfizer Global Product Development, in a statement.

PALLAS is an international, multicenter, randomized, open-label phase 3 study (NCT02513394) of 5796 participants who received oral palbociclib 125 mg once daily either with or without standard adjuvant endocrine therapy for a minimum of 5 years. In addition to iDFS, the study is assessing the safety of palbociclib when administered for 2 years with adjuvant endocrine therapy compared with adjuvant endocrine therapy alone. The trial is active but no longer recruiting patients.

In terms of disease characteristics, patients were eligible for enrollment if they were at least 18 years of age with stage II or III disease, a histologically confirmed ER/PR positivity, HER2 negativity, and must have undergone breast surgery for the current malignancy. Patients were also required to have an ECOG performance status of 0 or 1 and adequate laboratory values at screening to enroll in the study. Patients who received certain prior therapies or had comorbidities that could interfere with palbociclib treatment were excluded from the study.

PALLAS originally sparked interest in the breast cancer field in 2016, when the study design was first presented as the companion trial to the positive PENELOPE-1 study. Failure to meet its primary end point represents a downward trajectory for palbociclib in this patient population, where prior success was observed in the phase 3 PALOMA-2 study of palbociclib plus letrozole versus placebo plus letrozole. In PALOMA-2, palbociclib plus letrozole achieved a median progression-free survival of 38 months versus 14.5 with the placebo control combination (HR, 0.56; P <.0001). This research ultimately led to the FDA approval of palbociclib for multiple indications. Palbociclib is approved in combination with an aromatase inhibitor as initial endocrine therapy in women who are postmenopausal, or in combination with fulvestrant in patients who progressed on prior endocrine therapy.

“Since its initial approval in 2015, Ibrance has helped change the treatment landscape for people with HR-positive, HER2-negative metastatic breast cancer,” Boshoff added.

To further investigate palbociclib as treatment of early-stage disease, the PENELOPE-B study (NCT01864746) is currently underway. PENELOPE-B is a phase 3 study of palbociclib versus placebo in patients with HR-positive, HER2-negative breast cancer after neoadjuvant chemotherapy.

_Reference:

_{Pfizer provides update on phase 3 pallas trial of Ibrance® (palbociclib) plus endocrine therapy in hr+, her2- early breast cancer. News release. Pfizer, Inc. May 29, 2020. Accessed June 1, 2020. https://bit.ly/2zJQmO6.}