PMID- 31217344 OWN - NLM STAT- MEDLINE DCOM- 20200901 LR - 20200901 IS - 1549-490X (Electronic) IS - 1083-7159 (Print) IS - 1083-7159 (Linking) VI - 24 IP - 12 DP - 2019 Dec TI - Palbociclib with Letrozole in Postmenopausal Women with ER+/HER2- Advanced Breast Cancer: Hematologic Safety Analysis of the Randomized PALOMA-2 Trial. PG - 1514-1525 LID - 10.1634/theoncologist.2019-0019 [doi] AB - BACKGROUND: PALOMA-2 confirmed that first-line palbociclib + letrozole improved progression-free survival (hazard ratio, 0.58; 95% confidence interval, 0.46-0.72) in postmenopausal women with estrogen receptor-positive (ER+)/human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer (ABC). This analysis evaluated palbociclib-associated hematologic adverse events (AEs) and provides insight on managing these AEs. MATERIALS AND METHODS: Postmenopausal women with ER+/HER2- ABC were randomly assigned 2:1 to letrozole (2.5 mg daily continuously) plus oral palbociclib (125 mg daily; 3 weeks on/1 week off) or placebo. Safety assessments were performed at baseline, days 1 and 15 (first two cycles) and day 1 of subsequent cycles, and included white blood cell, platelet, and absolute neutrophil count (ANC). RESULTS: PALOMA-2 randomized 666 women to palbociclib + letrozole (n = 444) or placebo + letrozole (n = 222). Neutropenia was the most common AE (95.3%) with palbociclib (grade 3, 55.6%; grade 4, 11.5%) and was managed by dose modifications; progression-free survival was similar between patients who experienced grade >/= 3 neutropenia versus those who did not. Median (range) time to onset of neutropenia with palbociclib + letrozole was 15 (12-700) days (grade >/= 3, 28.0 [12-854] days); median duration of each neutropenia episode grade >/= 3 was 7.0 days. Asian ethnicity and low baseline ANC were associated with increased risk of grade 3/4 neutropenia with palbociclib (p < .001). CONCLUSION: Palbociclib + letrozole was generally well tolerated. Neutropenia, the most frequently reported AE in women with ER+/HER2- ABC, was mostly transient and manageable by dose modifications in patients who experienced grade >/= 3 neutropenia, without appearing to compromise efficacy. (Pfizer; NCT01740427) IMPLICATIONS FOR PRACTICE: Palbociclib demonstrated an acceptable safety profile in PALOMA-2 in women with estrogen receptor-positive (ER+)/human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer (ABC) receiving first-line palbociclib + letrozole. Although hematologic adverse events (AEs) are typically expected with anticancer therapies and are often clinically significant, palbociclib-related hematologic AEs, particularly neutropenia (most frequent AE), were transient/manageable by dose reduction, interruption, or cycle delay, which is in contrast to the more profound neutropenia associated with chemotherapy. Palbociclib dose adjustments decreased hematologic AE severity without appearing to compromise efficacy, supporting palbociclib + letrozole as a first-line treatment for ER+/HER2- ABC. CI - (c) 2019 The Authors. The Oncologist published by Wiley Periodicals, Inc. on behalf of AlphaMed Press. FAU - Dieras, Veronique AU - Dieras V AD - Department of Medical Oncology, Centre Eugene Marquis, Rennes, France v.dieras@rennes.unicancer.fr. FAU - Harbeck, Nadia AU - Harbeck N AD - Brustzentrum der Universitat Munchen, Munich, Germany. FAU - Joy, Anil Abraham AU - Joy AA AD - Cross Cancer Institute, University of Alberta, Edmonton, Alberta, Canada. FAU - Gelmon, Karen AU - Gelmon K AD - British Columbia Cancer Agency, Vancouver, British Columbia, Canada. FAU - Ettl, Johannes AU - Ettl J AD - Frauenklinik und Poliklinik Klinikum rechts der Isar, Technische Universitat, Munchen, Munich, Germany. FAU - Verma, Sunil AU - Verma S AD - University of Calgary, Calgary, Alberta, Canada. FAU - Lu, Dongrui R AU - Lu DR AD - Pfizer Inc., La Jolla, California, USA. FAU - Gauthier, Eric AU - Gauthier E AD - Pfizer Inc., San Francisco, California, USA. FAU - Schnell, Patrick AU - Schnell P AD - Pfizer Inc., New York New York, USA. FAU - Mori, Ave AU - Mori A AD - Pfizer s.r.l., Milan, Italy. FAU - Rugo, Hope S AU - Rugo HS AD - University of California San Francisco Helen Diller Family Comprehensive Cancer Center, San Francisco, California, USA. FAU - Finn, Richard S AU - Finn RS AD - David Geffen School of Medicine at UCLA, Santa Monica, California, USA. LA - eng SI - ClinicalTrials.gov/NCT01740427 PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20190619 PL - England TA - Oncologist JT - The oncologist JID - 9607837 RN - 0 (Piperazines) RN - 0 (Pyridines) RN - 7LKK855W8I (Letrozole) RN - EC 2.7.10.1 (Receptor, ErbB-2) RN - G9ZF61LE7G (palbociclib) SB - IM MH - Antineoplastic Combined Chemotherapy Protocols/pharmacology/*therapeutic use MH - Breast Neoplasms/*drug therapy MH - Female MH - Humans MH - Letrozole/pharmacology/*therapeutic use MH - Piperazines/pharmacology/*therapeutic use MH - Postmenopause MH - Pyridines/pharmacology/*therapeutic use MH - Receptor, ErbB-2/*metabolism PMC - PMC6975938 OTO - NOTNLM OT - Breast cancer OT - Hematologic OT - Neutropenia OT - Palbociclib OT - Safety COIS- Disclosures of potential conflicts of interest may be found at the end of this article. EDAT- 2019/06/21 06:00 MHDA- 2020/09/02 06:00 PMCR- 2019/06/19 CRDT- 2019/06/21 06:00 PHST- 2019/01/07 00:00 [received] PHST- 2019/05/01 00:00 [accepted] PHST- 2019/06/21 06:00 [pubmed] PHST- 2020/09/02 06:00 [medline] PHST- 2019/06/21 06:00 [entrez] PHST- 2019/06/19 00:00 [pmc-release] AID - theoncologist.2019-0019 [pii] AID - ONCO13002 [pii] AID - 10.1634/theoncologist.2019-0019 [doi] PST - ppublish SO - Oncologist. 2019 Dec;24(12):1514-1525. doi: 10.1634/theoncologist.2019-0019. Epub 2019 Jun 19.