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.

Although the risk of extravasation of a chemotherapy (anticancer) medication is low, the complications associated with these events can have a significant impact on morbidity and health care costs. Institutions that administer anticancer agents should ideally have a current guideline on the proper management of the inadvertent administration of these toxic medications into tissues surrounding blood vessels. It is imperative that the health care team involved in administering drugs used to treat cancer be educated on the risk factors, preventative strategies and treatment of anticancer extravasations, as well as practice safe and proper administration techniques. Anticancer agents are generally divided into classes based on their ability to cause tissue damage. The review of current published guidelines and available literature reveals a lack of consensus on how these medications should be classified. In addition, many recently approved drugs for the treatment of cancer may lack data to support their classification and management of extravasation events. The treatment of the majority of extravasations of anticancer agents involves nonpharmacological measures, potentially in the ambulatory care setting. Antidotes are available for the extravasation of a minority of vesicant agents in order to mitigate tissue damage. Due to the limited data and lack of consensus in published guidelines, a working group was established to put forth an institutional guideline on the management of anticancer extravasations.

No abstract

Background: Despite the high rates of neutropenia observed in the PALOMA studies, the incidence of neutropenic fevers remained low. The safety analysis from the PALOMA-3 trial showed no difference in PFS among pts who had dose reductions or delays secondary to neutropenia. We conducted a retrospective study to analyze the impact of dose delays and reductions on toxicity and progression free survival (PFS) in pts receiving palbociclib as standard of care. Methods: Pts with metastatic ER positive breast cancer receiving palbociclib in any line of therapy were identified from a cohort at MD Anderson Cancer Center. Clinical, demographic, baseline labs, comorbidities and recurrence data were collected. Dose delays, dose reductions, and toxicities were recorded up to the first 6 cycles of palbociclib. Early dose delays and reductions were defined as events occurring during the first 2 cycles of palbociclib while late events were defined as cycles 3-6. Data was analyzed using Fischer's exact test for categorized variables and T test/Wilcoxon rank-sum test for continuous variables. PFS was analyzed using the Kaplan Meier method and Cox model was used to analyze factors associated with PFS. Results: 344 pts who met eligibility criteria were included in the analysis. Pts receiving palbociclib on clinical trial were excluded. 109 (31.6%) pts received dose reductions and 153 (44.4%) experienced dose delays. The rate of neutropenic fever was low, occurring in 2.3% of all pts. There was a significant association between pts experiencing dose reductions and Hispanic race, baseline ANC, history of adjuvant endocrine therapy, adjuvant radiation therapy (XRT), and heart disease. History of adjuvant XRT, baseline ANC, and heart disease were associated with dose delays. Toxicities, including neutropenic fever, infections requiring antibiotics, and hospitalizations, were associated with dose reductions and dose delays. Median PFS for the cohort was 263.5 days. There was no significant association between early dose reductions or delays with PFS. Pts experiencing late dose delays (hazard ratio [HR], 0.4, P=0.0001) and reductions (HR, 0.4, P=0.0005) had a significantly longer PFS. Median PFS for pts without late dose delays was 228 days compared to 313.5 days for pts with late dose delays. Median PFS for pts without late dose reductions was 246 days compared to 305.5 days for pts with late dose reductions. In the multivariable analysis, liver metastasis, metastatic line, and higher tumor grade were associated with worse PFS. Pts receiving palbociclib and fulvestrant were found to have worse PFS than pts receiving palbociclib and letrozole. Conclusions: Similar to the PALOMA trials, this study found that while the rate of toxicities such as neutropenic fever were low, dose reductions and delays were common. In pts receiving palbociclib as standard of care, pts with late dose reductions and delays had a longer PFS than those without dose reductions and delays. It is reassuring that the PFS was not negatively affected in pts with dose reductions and delays. As use of palbociclib as standard of care becomes more common, further larger retrospective studies are warranted to examine the impact of dose delays and reductions. Citation Format: Clifton KK, Kimmel J, Yi M, Chad B, Litton J, Debu T, Meghan K. The impact of dose delays and reductions on toxicity and progression free survival (PFS) in patients receiving palbociclib [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P3-11-03.

No abstract