US-based pharmaceutical firm Pfizer has released promising results from its PALOMA-1 study, a randomised Phase II trial of palbociclib (PD-0332991) in combination with letrozole.
The company said that PALOMA-1 met its primary endpoint by prolonging progression-free survival (PFS) compared with letrozole alone in post-menopausal women with estrogen receptor positive (ER+), human epidermal growth factor receptor 2 negative (HER2-) locally advanced or metastatic breast cancer.
In women treated with palbociclib-letrozole combination, the median PFS was 20.2 months, a significant improvement compared to the 10.2 months of PFS in women who received letrozole alone.
Pfizer Oncology senior vice-president of clinical development and medical affairs Mace Rothenberg said the results show the potential of palbociclib to be a major advance in the treatment of women with this type of advanced breast cancer.
"We are proud to be at the forefront of research and development with respect to this promising new class of investigational anticancer agents and have initiated a broad clinical development programme for palbociclib that includes breast and non-breast cancers," Rothenberg said.
The company said that final results for the secondary efficacy endpoints of duration of treatment and clinical benefit rate showed superiority in the combination arm compared to the letrozole-only arm.
Under the PALOMA-1 study protocol, an initial assessment of overall survival (OS), a secondary endpoint, was also carried out.
Based on the events at the time of evaluation, a median OS of 37.5 months was observed in the combination arm versus 33.3 months for those who received letrozole alone, a difference of 4.2 months.
The palbociclib-letrozole combination was well-tolerated and the safety profile of the combination was consistent with previously reported data.
Common adverse events in the combination arm were neutropenia, leukopenia, fatigue and anaemia.
In April 2013, palbociclib got FDA breakthrough therapy designation for the initial treatment of women with advanced or metastatic ER+, HER2- breast cancer.
The breakthrough status was based on interim data from the PALOMA-1 trial, a multi-centre trial with 101 global sites participating.
PALOMA-1 is a Phase II trial designed to evaluate PFS in post-menopausal women with ER+, HER2- advanced breast cancer receiving palbociclib (125mg once daily for three out of four weeks in repeated cycles) in combination with letrozole versus letrozole alone (2.5mg once daily on a continuous regimen).
The trial consisted of two parts and the first part enrolled 66 patients with ER+, HER2- advanced breast cancer, while the second part enrolled 99 additional patients whose tumours were selected for presence of biomarkers: cyclin D1 amplification and/or p16 loss.
The trial was carried out in collaboration with the Jonsson Cancer Center's Revlon/UCLA Women's Cancer Research Program, led by Dr Dennis Slamon.