PALOMA-2: Neutropenia (NP) patterns in patients (Pts) with estrogen receptor−positive (ER+)/human epidermal growth factor receptor 2−negative (HER2–) first-line advanced breast cancer (ABC) receiving palbociclib + letrozole (P+L)

Abstract

Background: PALOMA‐2 demonstrated efficacy of P+L vs placebo (PBO)+ L inptswith treatment‐naive ER+/HER2‐ ABC (Finn NEJM 2016).We describe clinical patterns of hematologic adverse events (AEs),with an emphasis on NP, in pts receiving P+L. Methods: Postmenopausal women (N=666) with no prior systemic therapy for ABC were randomized 2:1 to receive P+L (P, 125 mg/d, 3 wk on/1 wk off; L, 2.5 mg/d continuously) or PBO+L (L, 2.5 mg/d continuously) until disease progression, unacceptable toxicity, or consent withdrawal. Hematological AEs are reported based on lab results. Results: As of 2/26/2016, median follow‐up was 23.0 mo in pts receiving P+L (n=444). Median age of P+L pts was 62.0 (range, 30‐89) years; ECOG status was 0, 1, and 2 in 57.9%, 40.1%, and 2.0%, respectively; and 213 (48.0%) received prior chemotherapy. 423 (95.3%) P+L pts experienced any grade (gr) NP, including 298 (70.4%) with gr 3/4 NP, manageable with dose modification. Among pts with gr 3/4 NP, 65 (15.4%), 41 (9.7%), and 192 (45.4%) experienced 1, 2, or ≥ 3 episodes, respectively. 92 (20.7%) and 84 (18.9%) pts experienced 3‐5 episodes of any grade anemia and thrombocytopenia, respectively. Median (range) times to first episode of gr ≥ 3 NP, anemia, and thrombocytopenia were 28.0 d (12‐854 [median duration, 31.5]), 182.0 d (14‐760 [11.5]), and 283.5 d (21‐617 [26.5]), respectively. Although NP is associated with increased risk of infection, the rate of gr 3/4 infections was 3.5% in P+L pts with NP. Of pts with gr 3/4 NP, 68.8% did not have any overlapping infections. Febrile NP was reported in 1.8%of P+L pts and did not result in therapy discontinuation. In univariate analysis, risk of developing gr 3/4 NP was associated with Asian ethnicity (P=0.0002) and low baseline absolute neutrophil counts (P<0.0001). NP resulting in dose reduction or interruption had no impact on PFS. Conclusions: NP occurred early during therapy, and was manageable with dose modification. Febrile NP was reported in 1.8% of P+L pts and did not result in therapy discontinuation. Withholding dose, or dose reduction does not negatively impact PFS. Funding, Pfizer.