Retrospective Analysis of Treatment Patterns and Effectiveness of Palbociclib and Subsequent Regimens in Metastatic Breast Cancer.

Background: Cyclin-dependent kinase (CDK) 4/6 inhibitors are now the standard of care for hormone receptor-positive (HR+), HER2-negative (HER-) metastatic breast cancer (MBC). However, guidelines are lacking regarding their optimal sequencing with other available agents. This study examines physician practice patterns and treatment outcomes of palbociclib and subsequent therapies in a real-world setting. Methods: A retrospective chart review was conducted for consecutive patients with MBC who received palbociclib between February 2015 and August 2017 at the Alvin J. Siteman Cancer Center. Kaplan-Meier method was used to generate time-to-event curves and estimate median progression-free survival (mPFS). Log-rank test was used to compare differences. Results: A total of 200 patients, with a median age of 59.4 years and a follow-up of 19.5 months, were included. Palbociclib was most frequently combined with letrozole (73.5%), followed by fulvestrant (25%), anastrozole (1%), and tamoxifen (0.5%). Most patients received palbociclib in the endocrine-resistant setting (n=42, n=50, and n=108 in the first-, second-, and subsequent-line settings, respectively), and the fraction of patients receiving palbociclib as first- or second-line therapy increased in recent months (P=.0428). mPFS was 20.7, 12.8, and 4.0 months with palbociclib administered in the first-, second-, and subsequent-line settings, respectively (P<.0001). Incidences of grade 3/4 neutropenia (41.5%) and dose reductions (29%) were comparable to reports in the literature. Among patients whose disease progressed on palbociclib (n=104), the most frequent next-line treatment was capecitabine (n=21), followed by eribulin (n=16), nab-paclitaxel (n=15), and exemestane + everolimus (n=12). mPFS with hormone therapy alone or in combination with targeted agents (n=32) after first-, second-, and subsequent-line palbociclib was 17.0, 9.3, and 4.2 months, respectively (P=.04). mPFS with chemotherapy (n=70) was not reached, 4.7, and 4.1 months after first-, second-, and subsequent-line palbociclib, respectively (P=.56). Conclusions: Palbociclib is effective for HR+/HER2- MBC in real-world practice. Hormone therapy alone or in combination with targeted agents remains an effective option after palbociclib progression.

Coagulopathy does not protect against venous thromboembolism in hospitalized patients with chronic liver disease.

BACKGROUND: It is uncertain whether pathologically prolonged international normalized ratio (INR) seen in chronic liver disease (CLD) protects against venous thromboembolism (VTE). Previous studies reported VTE incidence of 0.5% to 1.9% in patients with CLD. We sought to evaluate VTE incidence among hospitalized patients with CLD according to INR levels. METHODS: This was a retrospective cohort study performed at a tertiary university hospital. We included all adult patients admitted with a primary diagnosis of CLD over a 7-year period. The primary outcome was the development of VTE during hospital stay. Patients were divided into quartiles according to their highest admission INR. VTE events and prophylaxis rates were compared among INR quartiles. RESULTS: During the allotted 7-year period, we included 190 patients. Of these, 12 developed VTE events, yielding a VTE incidence of 6.3%. There was no significant difference in the incidence of VTE between INR quartiles. Hospital mortality rates were higher in the higher INR quartiles than in the lower ones (P < .001), but hospital length of stay was not significantly different. Of the patients with documented VTE, one (4.2%) was Child-Pugh stage A, three (4.6%) were stage B, and eight (8.0%) were stage C (P = .602). VTE prophylaxis was not used in 75% of patients. CONCLUSIONS: An elevated INR in the setting of CLD does not appear to protect against the development of hospital-acquired VTE. The notion that "auto-anticoagulation" protects against VTE is unfounded. Use of DVT prophylaxis was extremely low in this population.