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.

Background: Bone is the most common site of metastasis in metastatic breast cancer patients. Notably, bone biopsy is considered technically challenging with concerns regarding yield and reproducibility of immunohistochemistry technique. Our goal was to assess tumor subtype concordance between breast and bone biopsies done in patients with bone only metastases. Methods: We identified patients followed at MD Anderson Cancer Center for at least 6 months from 01/01/1997 to 12/31/2015 with bone as first site of metastasis. Breast and bone biopsy immunohistochemistry was used to categorize tumor subtype with hormone receptor positive (HR+) defined as ER or PR >1%. The following four tumor subtypes were identified: luminal A-like (HR+, HER2-), luminal B-like (HR+, HER2+), triple negative (HR-, HER2-), and HER positive (HR-, HER2+). Results: We identified 805 bone only metastasis patients with positive bone biopsies, 395 (49%) of which had hormone receptor and HER2 characterization available. Of these 395 patients, 293 (74%) were luminal A-like, 44 (11%) were luminal B-like, 51 (13%) were triple negative, and 7 (2%) were HER2 positive. Of these patients, we identified 281 patients with tumor subtype data available for both primary breast biopsy and bone metastasis biopsy, of which 237 (84%) were concordant, while 44 (16%) were discordant (Table 1). Table 1. Concordance between breast and bone biopsies based on initial breast biopsy tumor subtypeBreast Biopsy Tumor Subtype (n = 281)Concordance with Bone Biopsy Tumor SubtypeDiscordant Bone Biopsy Tumor SubtypeLuminal A-like, HR+ HER2- (225/80%)Concordant: 199 (88%), Discordant: 26 (12%)10 Luminal B-like, 16 Triple negativeLuminal B-like, HR+ HER2+ (33/12%)Concordant: 19 (58%), Discordant: 14 (42%)11 Luminal A-like, 2 Triple negative, 1 HER2 positiveTriple negative, HR- HER2- (20/7%)Concordant: 16 (80%), Discordant: 4 (20%)3 Luminal A-like, 1 Luminal B-likeHER2 positive, HR- HER2+ (3/1%)Concordant: 3 (100%), Discordant: 0 (0%)NA Conclusions: When available, bone biopsy tumor subtype had significant concordance with breast biopsy tumor subtype in this large study of bone only metastasis patients. Discordant tumor subtype results were more common in patients with luminal B-like tumor subtype on initial breast biopsy. Citation Format: Parkes AM, Clifton KK, Al Awadhi A, Oke OC, Warneke CL, Litton JK, Hortobagyi GN. Tumor subtype concordance between breast and bone biopsies in bone only metastasis patients [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 P1-16-01.