The CDK4/6 inhibitor palbociclib combined with endocrine therapy has proven to prolong progression-free survival (PFS) in previously untreated and pretreated women with HR+/HER2- MBC. Few data are available regarding the performance of such a regimen outside the clinical trials, and there is the need to understand its performances in real world.


We report a multicenter real-life experience aimed to verify the patterns of treatment and outcome of palbociclib plus endocrine therapy in an unselected population of MBC patients (pts). The primary endpoint was clinical benefit rate (CBR: complete response [CR], partial response [PR], or stable disease for longer than 6 months [SD]); secondary aims were median progression-free survival (mPFS) and safety of the combination. Statistical analysis was performed to identify variables potentially predictive of outcomes. Patients received P at 125 mg daily, 3 wk on/1 wk off in a 28d cycle, combined with letrozole administered orally 2.5 mg on a continuous daily dosing schedule (cohort A) or Fulvestrant 500 mg (F500) i.m. q4wks with loading dose (cohort B); treatment was given until disease progression, toxicity or patient's refusal.


The study enrolled 150 postmenopausal pts (65 in cohort A, 85 in cohort B) treated from December 2016 to April 2018 at 4 Italian Institutions. Median age in the whole population was 62 years (range 47-79; mean age 59 years in cohort A, 64 in cohort B); 13 pts (20%) in cohort A and 23 pts (27%) in cohort B had de novo metastatic disease; 46% of pts in cohort A and 55% had visceral involvement, while 17% and 20% respectively had bone-only disease. The median number of prior lines was 2 in cohort A (range 1-3) and 3 (range 2-5) in cohort B, including ET (median 3) and chemotherapy (median 2); in cohort B 37 pts (43%) had previously received F 500, while 12% (cohort A) and 15% (cohort B) had been pretreated with everolimus. In cohort A a PR as best response was observed in 32% (20 pts), with 14 pts (23%) achieving SD lasting ≥ 6 months for a CBR of 52%. In cohort B CBR was 60%, with 25% PR, 48% SD lasting ≥ 6 months in 35 pts (41%).

The most common adverse events in both cohorts were neutropenia (grade 1-2 in 67%, grade 3-4 in 35%), grade 1 anemia (52%) and thrombocytopenia (34%), requiring dose reduction in 27% of cases. At a median follow-up of 12 months (range 1-16), mPFS was 6.3 months in cohort A and 5.5 months in cohort B. In both groups a better mPFS was observed in pts treated as ≤ 3rd versus > 3rd line: 9.6 versus 5.2 in cohort A (p=0.003), 8.8 versus 4.1 months in cohort B, respectively (p= 0.002). No significant outcome differences were observed according to prior endocrine therapy with F500 or everolimus, or dominant metastatic site.


Our real life data, in line with the results of reported clinical trials, indicate that palbociclib plus letrozolo or F500 is active and safe in HR+/HER2- MBC, also suggesting a better performance of the combinations in earlier treatment lines.

Citation Format: Palumbo R, Torrisi R, Quaquarini E, Sottotetti F, Gambaro A, Collovà E, Ferzi A, Fava S, Agostinetto E, Tagliaferri B, Licata L, Teragni C, Bernardo A. Patterns of treatment and outcome of palbociclib plus endocrine therapy in hormone receptor-positive (HR+)/HER2 receptor-negative (HER2-) metastatic breast cancer (MBC): A real life multicenter Italian study [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P6-18-28.