Progression-free survival (PFS) and toxicities of palbociclib in a geriatric population

Abstract

Purpose: Over 40% of newly diagnosed metastatic breast cancer patients are ≥ 70 years-old however this population is less likely to be represented in clinical trials. The objective of this study was to analyze PFS, dose reductions, dose delays and toxicity in a geriatric population receiving palbociclib in a non-trial setting.Methods: Patients with metastatic breast cancer receiving palbociclib in any line of therapy were identified from a cohort of 845 patients at a large academic institution. Dose delays, dose reductions, and toxicities were retrospectively extracted from the medical record. Data were analyzed using Fischer's exact test for categorized variables and T test/Wilcoxon rank-sum test for continuous variables. PFS and OS were analyzed using the Kaplan Meier method.Results: 605 patients who met eligibility criteria were included. 160 patients were ≥ 65 years-old and 92 patients were ≥ 70 years-old. Patients ≥ 70 had a significantly increased number of dose reductions (p=0.03) and dose delays (p=0.02) compared to the younger patients. There was no significant increase in toxicities, including neutropenic fever, infections, or hospitalizations, in the ≥ 70 cohort (p=0.3). The ≥ 70 cohort had a significantly improved PFS as compared to the younger cohort (p=0.02) however age was no longer a significant variable in the multivariate analysis.Conclusions: Palbociclib was well tolerated in the geriatric population and there was no difference in PFS between older and younger patients. These results are reassuring as palbociclib becomes the frontline standard of care therapy for patients.

Patterns of treatment and outcome of palbociclib plus endocrine therapy in hormone receptor-positive/HER2 receptor-negative metastatic breast cancer: a real-world multicentre Italian study

“…No substantial differences in incidence and severity of AEs were seen between the two groups of women receiving palbociclib combined with letrozole or fulvestrant, and no increased toxicity was observed in patients >65 years compared with a younger population, in line with the recently reported data on a large geriatric population receiving palpociclib in a non-trial setting. 43 Nevertheless, we experienced fewer dose reductions (17% of patients in the whole population, most frequently due to neutropenia), compared with randomised phase III trials (36% and 34% of patients in PALOMA-2 and PALOMA-3, respectively) even if we had more cycle delays, as often happens in clinical practice. As previously reported, this did not seem to affect treatment effectiveness.…”

Optimizing Palbociclib Therapy Across the Age Spectrum: Hypothetical, Illustrative Case Scenarios in HR+, HER2– Metastatic Breast Cancer

“…The teams caring for Grace and Hazel made certain both women understood the risk of neutropenia with palbociclib—including how it differs from chemotherapy-induced neutropenia—and encouraged them to monitor their temperature and report any instances of fever above 100.4°F ( Sammons et al, 2017 ; Thill & Schmidt, 2018 ; US Department of Health and Human Services, 2017 ). In keeping with clinical trial and real-world evidence of an increased risk of neutropenia in older patients ( Clifton et al, 2019 ), Hazel experienced persistent neutropenia and leukopenia, which were addressed through treatment delay and dose modification. Nonhematologic AEs in both patients were effectively addressed through supportive measures, including medication and lifestyle changes.…”

“…Subgroup analyses from the PALOMA trials and real-world data have demonstrated that the efficacy and safety of palbociclib-based combination therapy is consistent regardless of age or menopausal status ( Clifton et al, 2019 ; Cristofanilli et al, 2016 ; Pfizer Inc, 2019a ; Loibl et al, 2017 ; Rugo et al, 2018 ). As a result, 74-year-old Hazel and 36-year-old Grace were both prescribed the recommended palbociclib starting dose of 125 mg ( Pfizer Inc, 2019a ).…”

“…A pooled analysis of outcomes in older patients enrolled in the full PALOMA trial program found that palbociclib-based combination therapy improved progression-free survival (PFS) across all age groups, with no significant deterioration in well-being or quality of life ( Rugo et al, 2018 ). In addition, real-world data from a cohort of geriatric patients treated with palbociclib at the MD Anderson Cancer Center between January 2015 and October 2017 (N = 605; of whom 160 were aged > 65 years) found no significant differences in palbociclib-related toxicities between patients ≥ 65 years old and those ≥ 70 years old, although patients aged ≥ 70 years were more likely to require early dose reductions and dose delays ( Clifton et al, 2019 ).…”

Living with Metastatic Cancer: A Roadmap for Future Research

“…In a meta-analysis of Phase II and III randomized clinical trials, older patients treated with palbociclib were more likely to experience neutropenia, leukopenia, anemia, back pain, asthenia, and infections, whereas older patients treated with abemaciclib were more likely to experience neutropenia, leukopenia, anemia, and diarrhea [ 37 ]. Older patients have also been shown to have more dose reductions and delays than younger patients [ 38 ].…”