Palbociclib and endocrine therapy in fourth line and beyond for hormone receptor-positive HER2-negative advanced breast cancer: the UK compassionate access program experience

Abstract

Background Palbociclib is approved in 1st line for hormone receptor (HR)-positive HER2-negative advanced breast cancer (ABC). A Compassionate Access Program (CAP) previously allowed patients to receive it in 4th line. However, Palbociclib has not been specifically tested in this population. We aimed to determine the safety and efficacy profile of Palbociclib within the CAP across ten institutions in the United Kingdom.

Methods We retrospectively identified HR-positive HER2-negative ABC patients on the Palbociclib CAP between December 2015 and September 2017. Demographics, disease characteristics, prior treatments, blood tests, toxicities, treatment delays and responses were recorded. Simple statistics, Fisher's exact test, chi-squared method and Cox regression were used as appropriate.

Results 118 patients identified had median age of 59 (32-82). 97 (82.20%) were postmenopausal and 109 (92.37%) had ECOG Performance Status 0-1. 96 (81.36%) had visceral involvement, 19 (16.10%) bony only and 15 (12.71%) visceral only disease. Patients received a median 5 (range 3-11) prior lines of treatment and 3 (range 0-8) prior chemotherapy lines.

105 patients (89.74%) developed neutropenia (grade ?3 in 59 [56.19%]). 6 experienced febrile neutropenia (5.13%). 57 (48.72%) had a dose reduction, down to 100mg in 48 (41.03%) and 75mg in 9 (7.69%) due to hematologic toxicity in 46 (80.70%). Dose delays were in median 7 days long (range: 0-56). Palbociclib was discontinued due to disease progression in 97 (82.91%) and to toxicity in 5 (4.27%). Grade 3 neutropenia occurred in 45 patients (67.16%) who received ?3 and in 22 (32.84%) who received <3 prior chemotherapies (p 0.351).

Palbociclib produced clinical benefit rate (CBR) of 47.52% and overall response rate of 15.84% in 101 patients assessed. CBR was 45.45% with previous endocrine treatment (ET) progression-free survival (PFS) <6 months versus 49.12% if PFS ?6 months (p 0.714).

Overall, median PFS was 4.5 months (95% CI 3.7-5.9). The PFS seen in different subgroups showed no impact in relation to the number of lines of prior chemotherapy (<3 lines: 5.9 months [95% CI 3.7-11.0]; ?3 lines: 4.3 months [95% CI 3.3-5.5], p 0.159), but was numerically greater in those who had previous benefit from ET (PFS ?6 months: 5.9 months [95% CI 4.4-8.0]; <6 months: 3.7 months [95% CI 2.8-4.5], p. 0.055) or in those with bone only disease (bone only: 11.0 months [95% CI 2.3-not reached]; other sites involved: 4.4 months [95% CI 3.6-5.5], p 0.024).

Median OS was 15.8 months (95% CI 13.3-18.7) for the whole cohort and it was greater in patients who derived longer PFS from prior ET (?6 months: 18.1 months [95% CI 13.0-NR]; <6 months: 14.4 months [95% CI 7.7-18.3], p. 0.052).

Conclusions To date, this is the most extensive analysis of Palbociclib outcomes in ?4th-line setting. In this heavily pretreated population clinical benefit was confirmed particularly for endocrine-sensitive disease and predominantly involving the bones and in earlier lines of treatment. Grade ?3 neutropenia rates were similar to PALOMA trials, but the higher incidence of febrile neutropenia need to be carefully considered.