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Breast Cancer Res. 2016 Jun 28;18(1):67. doi: 10.1186/s13058-016-0721-5.

Efficacy and safety of palbociclib in combination with letrozole as first-line treatment of ER-positive, HER2-negative, advanced breast cancer: expanded analyses of subgroups from the randomized pivotal trial PALOMA-1/TRIO-18.

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Department of Medicine, Division of Hematology/Oncology, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, CA, USA.
Irish Cooperative Oncology Research Group, Dublin, Ireland.
Technical University of Munich, Munich, Germany.
University Hospital Mainz, Mainz, Germany.
Dnipropetrovsk Medical Academy, City Multiple-Discipline Clinical Hospital, Dnipropetrovsk, Ukraine.
Orszagos Onkologiai Intezet, Budapest, Hungary.
Petz Aladar Megyei Oktato Korhaz, Gyor, Hungary.
Department of Medical Oncology, Szent Margit Korhaz, Onkologia, Budapest, Hungary.
Comprehensive Blood and Cancer Center, Bakersfield, CA, USA.
Pfizer Oncology, La Jolla, CA, USA.
Pfizer Oncology, New York, NY, USA.
Pfizer Oncology, Groton, CT, USA.
Pfizer Oncology, Collegeville, PA, USA.
Department of Medicine, Division of Hematology/Oncology, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, CA, USA.



Palbociclib is an oral small-molecule inhibitor of cyclin-dependent kinases 4 and 6. In the randomized, open-label, phase II PALOMA-1/TRIO-18 trial, palbociclib in combination with letrozole improved progression-free survival (PFS) compared with letrozole alone as first-line treatment of estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative, advanced breast cancer (20.2 months versus 10.2 months; hazard ratio (HR) = 0.488, 95 % confidence interval (CI) 0.319-0.748; one-sided p = 0.0004). Grade 3-4 neutropenia was the most common adverse event (AE) in the palbociclib + letrozole arm. We now present efficacy and safety analyses based on several specific patient and tumor characteristics, and present in detail the clinical patterns of neutropenia observed in the palbociclib + letrozole arm of the overall safety population.


Postmenopausal women (n = 165) with ER+, HER2-negative, advanced breast cancer who had not received any systemic treatment for their advanced disease were randomized 1:1 to receive either palbociclib in combination with letrozole or letrozole alone. Treatment continued until disease progression, unacceptable toxicity, consent withdrawal, or death. The primary endpoint was PFS. We now analyze the difference in PFS for the treatment populations by subgroups, including age, histological type, history of prior neoadjuvant/adjuvant systemic treatment, and sites of distant metastasis, using the Kaplan-Meier method. HR and 95 % CI are derived from a Cox proportional hazards regression model.


A clinically meaningful improvement in median PFS and clinical benefit response (CBR) rate was seen with palbociclib + letrozole in every subgroup evaluated. Grade 3-4 neutropenia was the most common AE with palbociclib + letrozole in all subgroups. Analysis of the frequency of neutropenia by grade during the first six cycles of treatment showed that there was a downward trend in Grade 3-4 neutropenia over time. Among those who experienced Grade 3-4 neutropenia, 71.7 % had no overlapping infections of any grade and none had overlapping Grade 3-4 infections.


The magnitude of clinical benefit seen with the addition of palbociclib to letrozole in improving both median PFS and CBR rate is consistent in nearly all subgroups analyzed, and consistent with that seen in the overall study population. The safety profile of the combination treatment in all subgroups was also comparable to that in the overall safety population of the study.


Breast cancer; Cyclin-dependent kinase; Estrogen receptor-positive; HER2-negative; Neutropenia

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