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

Abstract

Background: Cyclin-dependent kinase (CDK) 4/6 inhibitors are now standard of care for hormone receptor-positive (HR+), HER2-negative metastatic breast cancer (MBC). However, guidelines are lacking regarding their optimal sequencing with other available agents. This study aims to examine 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 MBC patients who received palbociclib between February 2015 and August 2017 at the 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: Two-hundred 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%). A majority of patients received palbociclib in the endocrine resistant setting (n=42, n=50, and n=108 in the first-, second-, and subsequent-line settings, respectively), the fraction of patients receiving palbociclib as the first- or second-line therapy increased in recent months (p=0.0428). The mPFS was 20.7, 12.8, and 4.0 months with palbociclib administered in the first-, second-, and subsequent-line settings, respectively (p<0.0001). Incidences of grade 3/4 neutropenia (41.5%) and dose reductions (29%) were comparable to literature report. Among patients who 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 plus everolimus (n=12). The mPFS with hormonal therapy or combinations (n=32) post first-, second-, and subsequent-line palbociclib was 17.0, 9.3, and 4.2 months, respectively (p=0.04). The mPFS with chemotherapy (n=70) was not-reached, 4.7, 4.1 months post first-line palbociclib, second-, and subsequent-line palbociclib, respectively (p=0.56). Conclusion: Palbociclib is effective for HR+HER2− MBC in real-world practice. Hormonal therapy or a combination with targeted agents remains an effective option following palbociclib progression.

CDK4/6 Inhibitors for Advanced Hormone Receptor–Positive Breast Cancer, 2019 and Beyond

“…Importantly, combination therapy with fulvestrant was not approved until 2016; therefore, most of the patients included in the analysis were treated with palbociclib and letrozole. 5 As may be expected, use changed over the course of the analysis, and early use may not be reflective of current use of CDK4/6 inhibitors. Over time, more patients were treated in the first-line setting and fewer in later lines.…”

“…Over time, more patients were treated in the first-line setting and fewer in later lines. 5 As Xi et al acknowledge, this observation is likely related to the treatment of patients whose disease had progressed on endocrine therapy but who did not have prior access to palbociclib in the first-line setting. It is also likely that physicians became more comfortable with treatment earlier in the disease course as they gained experience with the drug and the management of related toxicities.…”

“…However, dose reductions were similar, performed in approximately 30% of patients. 2,3,5 It is unclear whether the recommended starting dose of 125 mg that was administered in the phase III studies was prescribed in all patients; it is possible that physicians chose to start certain patients at a lower dose, resulting in lower grades of neutropenia.…”

“…The OS improvement in endocrinesensitive breast cancers observed in PALOMA-3 4 is reassuring. Patients in the retrospective study by Xi et al 5 received a variety of subsequent therapies, including both chemotherapy and endocrine therapy regimens. Endocrine therapy-based regimens were efficacious despite prior CDK4/6 inhibitor therapy.…”

“…However, prespecified subgroup analysis demonstrated a statistically significant absolute benefit of 10 months (39.7 vs 29.7 months; HR, 0.46; 95% CI, 0.36-0.59) in patients who had previously been sensitive to endocrine therapy. 4 In the article by Xi et al 5 elsewhere in this issue, the authors report on a retrospective analysis of palbociclib combined with endocrine therapy for metastatic HR1 breast cancer at a single academic institution. Although clinical trials are evaluating the management of patients after disease progression on CDK4/6 See page 141 for related article.…”