Johannes Ettl1, Seock-Ah Im2, Jungsil Ro3, Norikazu Masuda4, Marco Colleoni5, Patrick Schnell6, Eustratios Bananis6, Dongrui R Lu7, Massimo Cristofanilli8, Hope S Rugo9, Richard S Finn10. 1. Department of Obstetrics and Gynecology, Klinikum rechts der Isar, Technische Universität München, Ismaningerstr. 22, 81675, Munich, Germany. johannes.ettl@tum.de. 2. Seoul National University Hospital Cancer Research Institute, Seoul National University College of Medicine, Seoul, South Korea. 3. National Cancer Center, Goyang-si, South Korea. 4. National Hospital Organization Osaka National Hospital, Osaka City, Japan. 5. IEO, European Institute of Oncology, IRCCS, Milan, Italy. 6. Pfizer Oncology, New York, NY, USA. 7. Pfizer Inc, La Jolla, CA, USA. 8. Robert H. Lurie Cancer Center of Northwestern University, Feinberg School of Medicine, Chicago, IL, USA. 9. University of California San Francisco Helen Diller Family Comprehensive Cancer Center, San Francisco, CA, USA. 10. David Geffen School of Medicine at University of California Los Angeles, Los Angeles, CA, USA.
Abstract
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 plusletrozole or letrozole alone. PALOMA-2 was a phase 3, double-blind study of postmenopausal patients untreated for ABC receiving palbociclib plusletrozole 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, receivingpalbociclib 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.
RCT Entities:
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.
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Authors: Maria Alice Franzoi; Daniel Eiger; Lieveke Ameye; Noam Ponde; Rafael Caparica; Claudia De Angelis; Mariana Brandão; Christine Desmedt; Serena Di Cosimo; Nuria Kotecki; Matteo Lambertini; Ahmad Awada; Martine Piccart; Evandro de Azambuja Journal: J Natl Cancer Inst Date: 2021-04-06 Impact factor: 13.506
Authors: Richard S Finn; Hope S Rugo; Karen A Gelmon; Massimo Cristofanilli; Marco Colleoni; Sherene Loi; Patrick Schnell; Dongrui R Lu; Kathy Puyana Theall; Ave Mori; Eric Gauthier; Eustratios Bananis; Nicholas C Turner; Véronique Diéras Journal: Oncologist Date: 2021-03-10