Abstract P3-11-03: The impact of dose delays and reductions on toxicity and progression free survival (PFS) in patients receiving palbociclib

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.

First-Line Treatment with a Cyclin-Dependent Kinase 4/6 Inhibitor Plus an Aromatase Inhibitor for Metastatic Breast Cancer in Alberta

“…We found that dose reduction was significantly associated with worse PFS. This is in contrast to what has been observed in randomized trials [ 35 , 36 , 37 , 38 ] and some other retrospective studies [ 39 , 40 ]. Upfront dose reduction and subsequent dose reduction due to toxicity could reflect poor patient-related prognostic factors, such as less favourable performance status and comorbidities.…”

Palbociclib plus endocrine therapy in HER2 negative, hormonal receptor‐positive, advanced breast cancer: A real‐world experience

“…In our study, the efficacy of palbociclib treatment was not affected by dose reductions, most frequently due to neutropenia. Our results are fully consistent with those from a retrospective report from the MD Anderson Cancer Center, which investigated the impact of dose delays and reductions on PFS in 334 patients receiving palbociclib in real‐life setting (Clifton et al, ). In terms of safety, no new issues emerged in our patient population and no cumulative toxicity was reported.…”

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

“…As previously reported, this did not seem to affect treatment effectiveness. [14][15][16]36,43,44 The strength of the present experience is the prospective evaluation in a large cohort of unselected breast cancer patients of palbociclib plus ET combinations in a real-world setting with a long follow-up time. Our data also provide information concerning the prior treatment with fulvestrant and/or everolimus, confirming no detrimental effect of both the agents on palbociclib-treated patients.…”