Palbociclib in daily clinical use: Real world experience of the breast center at the University Hospital Munich
Authors: A. Hester, A. Koenig, F. Dobler, T. Degenhardt, H. Heidegger-Steger, A.-G. Kurt, S. Kahlert, S. Mahner, N. Harbeck, R. Wuerstlein
Journal: Annals of Oncology (2019)

Background: Since its approval in Europe in November 2016, the CDK4/6 inhibitor palbociclib (PA) has been widely used for treatment of hormone receptor-positive (HR+) metastatic breast cancer (MBC). This study evaluates as a quality assurance measure the treatment with PA at the breast center of the University of Munich (LMU). Methods: Patients (pts) who started PA-treatment for HR+ MBC between 9/16-9/18 (n = 75) were retrospectively included. Data were obtained from pt medical files in 12/18 (54.7 % still under ongoing therapy). Statistical analyses were performed using Chi-squared-test and Kaplan-Meier-estimates. Results: Median age was 62 years; the main localization of metastases was bone (77.3 % of all pts, lymphatic 41.3 %, liver 36 %). 72 % received PA as 1st or 2nd line therapy for MBC, most had a history (adjuvant or in MBC) of at least one endocrine therapy (78.7 %) or chemotherapy (64.4 %). Most pts (50.7 %) received fulvestrant (letrozole 44 %, exemestane 5.3 %) and a starting dose of 125 mg PA (77.3 %). Dose reduction (DR) to 100 or 75 mg PA occurred in 52.1 % and 24 % of all pts - mainly due to grade 3 neutropenia (shown in 64 % of all pts, reason for 86.7 % of 1st and 88.9 % of 2nd DR). Main non-hematological complications were fatigue (41.3 %) and gastrointestinal symptoms (40 %), especially in the first therapy cycles with improvement over time. Complications and need for DR did not significantly correlate with localization of metastasis, therapy line or prior therapies. 45.3 % stopped PA-therapy during the observation period, mainly (85.3 %) due to progression. Median progression-free survival (PFS) estimated by Kaplan-Meier was 16 (95 % CI 9.1 - 22.9) months. Estimated median PFS was significantly shorter in pts with liver metastasis (7 months, without liver metastasis median not reached, p = 0.01), if PA was used in 3rd line or later (9 vs. 18 months, p = 0.01) and in pts receiving fulvestrant compared to letrozole (11 months, in letrozole therapy median not reached; p = 0.04). Conclusions: Our data show that in daily clinical use, PA is a well-tolerated therapy for MBC with grade 3 neutropenia as the main complication. Pts with liver metastasis should be monitored carefully as progression seemed to occur earlier in this group. Legal entity responsible for the study: Department of Obstetrics and Gynaecology, Breast Center and CCC Munich, University Hospital, LMU Munich. Funding: Has not received any funding. Disclosure: A. Hester: Research grants: The "Walter Schulz Stiftung"; Speaker, advisory board honorarium: Roche, Germany; Travel and accommodation costs, honorarium for symposium: Pfizer. T. Degenhardt: Honoraria for consultant activity: Pfizer; Travel support: Celgene S. Mahner: Research support, advisory board, honoraria, travel expenses: AstraZeneca, Clovis, Medac, MSD, PharmaMar, Roche, Sensor Kinesis, Tesaro, Teva. N. Harbeck: Honoraria for consulting / Lectures: Novartis, Lilly, Pfizer. R. Wuerstlein: Honoraria, consulting: Agendia, Amgen, AstraZeneca, BI, Carl Zeiss, Celgene, Daiichi-Sankyo, Eisai, Genomic Health, GSK, Hexal, Lilly, MSD, Mundipharma, NanoString, Novartis, Odonate, Paxman, Palleos, Pfizer, Pierre Fabre, PBYI, Riemser, Roche, Sandoz/Hexal, SGEN, Tesaro, Teva. All other authors have declared no conflicts of interest.