Abstract P4-13-05: Safety results of the US expanded access program (EAP) of palbociclib in combination with letrozole as treatment of post-menopausal women with hormone-receptor-positive (HR+), HER2-negative (HER2-) advanced breast cancer (ABC) for whom letrozole therapy is deemed appropriate
Authors: Stearns V , Smith II JW , Patel R , Lu D , Perkins JJ , Cotter MJ , Brufsky AM 
Published: May 2016

Abstract
Background: In the Phase I/II PALOMA-1 trial, a study in women with estrogen receptor (ER) positive advanced breast cancer (ABC) receiving initial therapy for their metastatic disease, combination of the CDK4/6 inhibitor palbociclib with letrozole improved progression free survival compared to letrozole. The aim of this open-label, single-arm EAP was to provide appropriate patients (pts) with ABC access to palbociclib pending marketing approval in the United States.
Methods: In the EAP, a total of 242 pts with HR+/HER2- ABC were treated at 42 sites in the US. Pts received palbociclib 125 mg/d (3 weeks on, 1 week off) in combination with letrozole 2.5 mg/d (continuous daily dosing) until disease progression, intolerable adverse event (AE), or commercial availability. AEs and serious AEs (SAEs) were assessed every cycle. Complete blood counts were assessed on day 1 and day 14 of the first two cycles and then at the beginning of each cycle thereafter. Tumor assessments were collected by investigators as per routine clinical practice.
Results: In this early analysis, we describe an initial cohort of 97 pts, with data collected during the first 3 months of study. Median duration of therapy was 31 days. Mean age was 62 yr (range 29-89). Baseline ECOG PS was 0, 1 or 2 in 36%, 49%, and 14% of pts, respectively. Common prior treatments (≥40% in any setting) included fulvestrant (59%), anastrozole (50%), paclitaxel (50%), exemestane (48%), cyclophosphamide (46%), tamoxifen (45%), doxorubicin (44%), and capecitabine (40%). Treatment-emergent AEs (TEAE; all grades) that occurred in greater than 10% of patients included neutropenia (28%), fatigue (19%), neutrophil count decreased (12%). Other hematologic TEAE rates included: anemia 9%, white blood cell count decreased 9% and thrombocytopenia 5%. All causality SAEs occurred in 6% of pts at the rate of 1 patient each for ankle fracture, constipation, disease progression, febrile neutropenia, lung infection, and pancytopenia. The rate of palbociclib dose reduction due to a TEAE was 4%. The rate of temporary delay of palbociclib due to TEAE was 36%. TEAEs leading to permanent discontinuation occurred in 1% of pts (Grade 3 nausea & vomiting). Grade 3 or 4 TEAEs were reported in 42% of pts, including neutropenia (Grade 3: 24%, Grade 4: 2%). There were no fatal outcomes due to TEAEs. This early data will be updated for final conference presentation to include the complete patient cohort and updated duration of therapy on study drug.
Conclusions: In this population of pts with HR+/HER2- ABC, palbociclib in combination with letrozole was well tolerated. Analysis of this early cohort indicates that the safety profile was consistent with that seen in the PALOMA-1 trial.
Clinical trial information: NCT02142868
Funding Source: Pfizer.
Citation Format: Stearns V, Smith II JW, Patel R, Lu D, Perkins JJ, Cotter MJ, Brufsky AM. Safety results of the US expanded access program (EAP) of palbociclib in combination with letrozole as treatment of post-menopausal women with hormone-receptor-positive (HR+), HER2-negative (HER2-) advanced breast cancer (ABC) for whom letrozole therapy is deemed appropriate. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P4-13-05.