PMID- 32164785 OWN - NLM STAT- MEDLINE DCOM- 20201001 LR - 20210816 IS - 1465-542X (Electronic) IS - 1465-5411 (Print) IS - 1465-5411 (Linking) VI - 22 IP - 1 DP - 2020 Mar 12 TI - Hematologic adverse events following palbociclib dose reduction in patients with hormone receptor-positive/human epidermal growth factor receptor 2-negative advanced breast cancer: pooled analysis from randomized phase 2 and 3 studies. PG - 27 LID - 10.1186/s13058-020-01263-0 [doi] LID - 27 AB - BACKGROUND: Palbociclib improves outcomes for women with hormone receptor-positive/human epidermal growth factor receptor 2-negative advanced breast cancer (HR+/HER2- ABC). Dose reductions are recommended for the management of hematologic toxicities. A previous pooled analysis from the PALOMA clinical trials showed that 36.9% of patients required dose reduction, predominantly during the first 6 months of treatment and with decreasing frequency during subsequent 28-day treatment cycles (C). Previous data have shown that palbociclib dose reductions do not affect efficacy. This pooled, post hoc analysis evaluated the frequency of hematologic adverse events (AEs) before and after palbociclib dose reduction in PALOMA-1, PALOMA-2, and PALOMA-3. METHODS: This analysis evaluated the frequency of hematologic AEs 30 days before dose reduction and during each subsequent treatment from C1 to C6 among patients who required palbociclib dose reduction. Data were pooled from 3 randomized studies. PALOMA-1 was a phase 2, open-label study of postmenopausal patients untreated for ABC receiving palbociclib plus letrozole or letrozole alone. PALOMA-2 was a phase 3, double-blind study of postmenopausal patients untreated for ABC receiving palbociclib plus letrozole or placebo plus letrozole. PALOMA-3 was a phase 3, double-blind study of pre/perimenopausal or postmenopausal patients, whose disease progressed on prior endocrine therapy, receiving palbociclib plus fulvestrant or placebo plus fulvestrant. RESULTS: A total of 311 (35.5%) patients with HR+/HER2- ABC required a palbociclib dose reduction (93.6% due to AEs) from 125 to 100 mg. Mean patient age was 59.9 years, and 46.9% of patients had visceral disease. Median time to dose reduction was 70 days. The majority of dose reductions occurred within 3 months of starting palbociclib treatment. Incidences of all-grade and grades 3/4 hematologic AEs were lower following dose reduction. CONCLUSIONS: A decrease in frequency and severity of hematologic AEs, including febrile neutropenia, following palbociclib dose reduction was observed, supporting the recommended use of dose reduction in AE management. TRIAL REGISTRATION: These studies were sponsored by Pfizer. ClinicalTrials.gov: NCT00721409; registration date July 24, 2008. ClinicalTrials.gov: NCT01740427; registration date December 4, 2012. ClinicalTrials.gov: NCT01942135; registration date September 13, 2013. FAU - Ettl, Johannes AU - Ettl J AD - Department of Obstetrics and Gynecology, Klinikum rechts der Isar, Technische Universitat Munchen, Ismaningerstr. 22, 81675, Munich, Germany. johannes.ettl@tum.de. FAU - Im, Seock-Ah AU - Im SA AD - Seoul National University Hospital Cancer Research Institute, Seoul National University College of Medicine, Seoul, South Korea. FAU - Ro, Jungsil AU - Ro J AD - National Cancer Center, Goyang-si, South Korea. FAU - Masuda, Norikazu AU - Masuda N AD - National Hospital Organization Osaka National Hospital, Osaka City, Japan. FAU - Colleoni, Marco AU - Colleoni M AD - IEO, European Institute of Oncology, IRCCS, Milan, Italy. FAU - Schnell, Patrick AU - Schnell P AD - Pfizer Oncology, New York, NY, USA. FAU - Bananis, Eustratios AU - Bananis E AD - Pfizer Oncology, New York, NY, USA. FAU - Lu, Dongrui R AU - Lu DR AD - Pfizer Inc, La Jolla, CA, USA. FAU - Cristofanilli, Massimo AU - Cristofanilli M AD - Robert H. Lurie Cancer Center of Northwestern University, Feinberg School of Medicine, Chicago, IL, USA. FAU - Rugo, Hope S AU - Rugo HS AD - University of California San Francisco Helen Diller Family Comprehensive Cancer Center, San Francisco, CA, USA. FAU - Finn, Richard S AU - Finn RS AD - David Geffen School of Medicine at University of California Los Angeles, Los Angeles, CA, USA. LA - eng SI - ClinicalTrials.gov/NCT00721409 SI - ClinicalTrials.gov/NCT01740427 SI - ClinicalTrials.gov/NCT01942135 PT - Clinical Trial, Phase II PT - Clinical Trial, Phase III PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20200312 PL - England TA - Breast Cancer Res JT - Breast cancer research : BCR JID - 100927353 RN - 0 (Antineoplastic Agents) RN - 0 (ESR1 protein, human) RN - 0 (Estrogen Receptor alpha) RN - 0 (Piperazines) RN - 0 (Pyridines) RN - 0 (Receptors, Progesterone) RN - EC 2.7.10.1 (ERBB2 protein, human) RN - EC 2.7.10.1 (Receptor, ErbB-2) RN - G9ZF61LE7G (palbociclib) SB - IM MH - Adult MH - Aged MH - Aged, 80 and over MH - Antineoplastic Agents/*adverse effects MH - Breast Neoplasms/*drug therapy/*pathology MH - Dose-Response Relationship, Drug MH - Double-Blind Method MH - Estrogen Receptor alpha/*metabolism MH - Female MH - Hematologic Diseases/*chemically induced MH - Humans MH - Middle Aged MH - Neoplasm Staging MH - Patient Safety MH - Piperazines/*adverse effects MH - Pyridines/*adverse effects MH - Receptor, ErbB-2/*metabolism MH - Receptors, Progesterone/metabolism MH - Treatment Outcome PMC - PMC7068918 OTO - NOTNLM OT - Adverse event management OT - Dose modification OT - Dose reductions OT - Neutropenia OT - Palbociclib COIS- JE received consulting fees from Eli Lilly, Novartis, Pfizer, Roche, and Eisai; performed contracted research for Celgene; and received honoraria and travel support from Celgene, Eli Lilly, Novartis, Pfizer, Roche, and TEVA. S-AI has advisory roles with AstraZeneca, Amgen, Hanmi Corp, Roche, Pfizer, and Novartis and has received grants from AstraZeneca and Pfizer. NM reports honoraria from Chugai, AstraZeneca, Pfizer, and Takeda and research funds from Chugai, AstraZeneca, Kyowa-Kirin, MSD, Novartis, Pfizer, Eli Lilly, and Daiichi-Sankyo. MCo reports a consulting or advisory role for Pfizer, OBI Pharma, AstraZeneca, Novartis, Pierre Fabre, Puma, and Celldex. MCr reports personal fees from Pfizer, Novartis, and Merus. HSR's institution received research funding from Plexxikon, Macrogenics, OBI Pharma, Eisai, Pfizer, Novartis, Eli Lilly, Roche, and Merck. RSF received consulting fees from Pfizer, Bayer, Novartis, Bristol-Myers Squibb, and Merck as well as other research funding from Pfizer and honoraria from Bayer, Pfizer, Bristol-Myers Squibb, Novartis, Eisai, and Eli Lilly. PS, EB, and DRL are employees of and own stock in Pfizer. JR declares that there are no competing interests. EDAT- 2020/03/14 06:00 MHDA- 2020/10/02 06:00 PMCR- 2020/03/12 CRDT- 2020/03/14 06:00 PHST- 2019/11/06 00:00 [received] PHST- 2020/02/26 00:00 [accepted] PHST- 2020/03/14 06:00 [entrez] PHST- 2020/03/14 06:00 [pubmed] PHST- 2020/10/02 06:00 [medline] PHST- 2020/03/12 00:00 [pmc-release] AID - 10.1186/s13058-020-01263-0 [pii] AID - 1263 [pii] AID - 10.1186/s13058-020-01263-0 [doi] PST - epublish SO - Breast Cancer Res. 2020 Mar 12;22(1):27. doi: 10.1186/s13058-020-01263-0.