Real-World Evidence Supports Effectiveness of First-Line IBRANCE® (Palbociclib) Combination Therapy in HR+, HER2- Metastatic Breast Cancer

First large-scale comparative effectiveness analysis of a CDK 4/6 inhibitor plus letrozole evaluating progression-free and overall survival versus letrozole alone

Pfizer Inc. (NYSE:PFE) today announced the peer-reviewed publication of real-world evidence (RWE) demonstrating that first-line therapy with IBRANCE® (palbociclib) in combination with letrozole was associated with improved real-world progression-free survival (rwPFS) and overall survival (OS) in women with hormone receptor-positive (HR+), human epidermal growth factor 2-negative (HER2-) metastatic breast cancer (mBC) compared with letrozole alone. These findings represent the first comprehensive comparative effectiveness analysis of survival outcomes for a CDK 4/6 inhibitor in routine clinical practice and were published online in Breast Cancer Research.

At a median follow-up of approximately two years and after balancing for baseline demographic and clinical characteristics, median rwPFS was 20.0 months with IBRANCE plus letrozole versus 11.9 months with letrozole alone (HR 0.58: 95% CI, 0.49 to 0.69; p<0.0001) in this observational, retrospective real-world analysis. Median OS was not reached among patients in the IBRANCE group and was 43.1 months among patients in the letrozole group (HR 0.66: 95% CI, 0.53 to 0.82; P=0.0002). These findings represent a 42% reduction in the risk of progression and a 34% reduction in the risk of death.

“Real-world evidence is woven into the fabric of how we innovate and advance care for patients with breast cancer, supporting our randomized clinical trials,” said Chris Boshoff, M.D., Ph.D., Chief Development Officer, Oncology, Pfizer Global Product Development. “With more than six years of patient experience, a positive benefit-risk profile, strong clinical data and robust real-world data, the totality of evidence solidifies the role of IBRANCE plus endocrine therapy as a treatment for patients with HR+, HER2- metastatic breast cancer.”

The analysis also showed the two-year OS rate was 78.3% in the IBRANCE group and 68.0% with letrozole. The rwPFS and OS benefits were generally consistent across all subgroups, including younger patients (18-50 years of age) and site or extent of metastases.

“Real-world evidence is increasingly used to complement traditional randomized clinical trial data to better understand a therapy’s effectiveness in routine clinical practice and inform treatment decisions,” said Angela DeMichele, M.D., lead researcher and Professor in Breast Cancer Excellence in the Perelman School of Medicine at the University of Pennsylvania. “The findings from this landmark real-world study align with the positive impact that I have seen in my own patients treated with IBRANCE combination therapy.”

The data for this retrospective observational analysis was collected from the Flatiron Health de-identified longitudinal database, which includes patient records from Flatiron’s network of more than 280 community cancer clinics and partnerships with major academic cancer centers across the U.S. This real-world cohort includes more than 1,400 women with HR+, HER2- mBC with any extent of visceral disease. Safety data were not collected as part of this analysis.

The data from this real-world analysis is consistent with available data from the Phase 3 PALOMA-2 trial, which studied IBRANCE plus letrozole versus placebo plus letrozole as initial endocrine-based therapy in post-menopausal women with estrogen-receptor positive (ER+), HER2- mBC. However, this observational analysis differs from the randomized clinical trial in several ways. The studies have different endpoints and there are inherent limitations in real-world observational studies, including lack of randomization, lack of uniform timing or type of clinical assessments and challenges with missing data. OS data is being collected in the PALOMA-2 randomized clinical trial but is not yet mature.