Abstract P5-14-08: Predictors of relative dose intensity and early dose reduction in patients with metastatic breast cancer treated with palbociclib and endocrine therapy
Authors: Pelizzari Giacomo , Bertoli Elisa , Giavarra Marco , Corvaja Carla , Gerratana Lorenzo , Basile Debora , Bartoletti Michele , Lisanti Camilla , Bortot Lucia , Buriolla Silvia , Garutti Mattia , Avoledo Debora , Bonotto Marta , Da Ros Lucia , Bolzonello Silvia , Mansutti Mauro , Nardo Paola Di , Fasola Gianpiero , Spazzapan Simon , Minisini Alessandro M , Puglisi Fabio 
Published: March 2020

Abstract
Background: The combination of endocrine therapy with the cyclin-dependent kinases 4/6 inhibitor palbociclib was proven to be effective for the treatment of hormone receptor (HR)-positive/HER2-negative metastatic breast cancer (MBC). Although generally well tolerated, treatment delays and dose reductions are frequently observed with palbociclib, mainly due to severe neutropenia. Predictors of palbociclib-related toxicities are still unknown, as well as the clinical relevance of its relative dose intensity (RDI). Henceforth, this study aimed to identify baseline clinicopathological features associated with a RDI &lt;75% and early dose reduction (within the first 3 months of treatment). Secondarily, we explored the impact of RDI &lt;75% and early dose reduction on progression-free survival.
Methods: We reviewed data of 150 consecutive patients with HR-positive/HER2-negative MBC patients treated with palbociclib at two Italian cancer centers from 2017 to 2019. Eligible patients must have received at least 3 cycles of treatment. Those who experienced early suspension due to unacceptable toxicities were still eligible. RDI was calculated as the ratio of actual dose intensity (cumulative administered dose/treatment duration) and planned dose intensity (cumulative planned dose/planned treatment duration). The association of both RDI &lt;75% and early dose reduction with baseline clinicopathological features was assessed using multivariate logistic regression. The following variables were investigated as predictors of dose reduction: de novo vs. recurrent MBC, prior chemotherapy, treatment line, associated endocrine therapy, performance status (PS), weight, renal clearance, hemoglobin level, absolute white blood cell (WBC) count, absolute neutrophils count and absolute platelet count. A ROC analysis was performed to identify the best cut-off for baseline weight in predicting a RDI &lt;75%, while continuous laboratory variables were dichotomized according to clinically relevant cut-offs.
Results: Overall, 142 patients were deemed eligible. Of these patients, 98 (69.0%) were treated with palbociclib plus fulvestrant, 44 (31.0%) with palbociclib plus aromatase inhibitors, and 73 (51.4%) in the first-line setting. The median number of administered palbociclib cycles was 8 (range: 1-24) and 61 patients (43.0%) required at least a first-level dose reduction (29 within 3 months). Furthermore, the median time to first dose reduction was 3.22 months, with neutropenia being responsible for 85.24% of first-level dose reductions. In the whole cohort, median RDI was 90.5% (95.1% for patients without dose reduction and 80% for those who had received a dose reduction). Notably, 28 patients (19.7%) experienced a RDI &lt;75%. Through multivariate logistic regression, baseline weight ≤66 kg (OR 3.01, 95% CI: 1.08-8.35, p=0.03) and WBC ≤4.5 × 109/L (OR 3.15, 95% CI: 1.08-9.12, p=0.03) were independently associated with a RDI &lt;75%. Moreover, baseline weight ≤66 kg was also significantly correlated with early dose reduction (OR 2.77, 95% CI: 1.09-7.01, p=0.03). After a median follow-up of 11.76 months, median PFS was 13.99 months. When exploring potential prognostic factors, neither a RDI &lt;75% (HR 1.01, 95% CI: 0.52-1.95, p=0.97) nor a dose reduction within the first 3 months (HR 1.39, 95% CI: 0.67-2.91, p=0.31) did significantly impact PFS.
Conclusions: In our analysis, baseline weight and WBC were statistically associated with a RDI &lt;75% in patients with MBC treated with palbociclib. Furthermore, baseline weight was also able to predict an early dose reduction in the study population. Lastly, early dose reduction and RDI &lt;75% did not impact PFS. Although the small sample size and the limited follow-up, our results warrant further investigation in specifically designed trials.
Citation Format: Giacomo Pelizzari, Elisa Bertoli, Marco Giavarra, Carla Corvaja, Lorenzo Gerratana, Debora Basile, Michele Bartoletti, Camilla Lisanti, Lucia Bortot, Silvia Buriolla, Mattia Garutti, Debora Avoledo, Marta Bonotto, Lucia Da Ros, Silvia Bolzonello, Mauro Mansutti, Paola Di Nardo, Gianpiero Fasola, Simon Spazzapan, Alessandro M Minisini, Fabio Puglisi. Predictors of relative dose intensity and early dose reduction in patients with metastatic breast cancer treated with palbociclib and endocrine therapy [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P5-14-08.