Abstract P5-21-11: Benefit from palbociclib and fulvestrant based on previous fulvestrant and/or everolimus treatment. Based on a cohort of over 200 patients treated in a French compassionate program

Abstract

Background: CDK4/6 inhibitors have been approved in the recent years for the treatment of advanced hormone receptor-positive breast cancer. For patients with resistance to previous endocrine therapy, the approval is based on the results of the PALOMA-3 trial testing palbociclib in addition to fulvestrant observing a progression-free survival (PFS) of 9.2 months. Nevertheless, in this study no previous treatment with fulvestrant was allowed and no information had been reported of efficacy after everolimus administration. Patients and methods: We collected information from patients treated with palbociclib + fulvestrant in the context of a French compassionate access. We aimed at determining the benefit of this treatment in a real population to provide information about PFS in non-selected patients as well as efficacy of palbociclib and fulvestrant in patients previously treated with fulvestrant and/or everolimus. Median PFS were assessed by Kaplan-Meier survival analysis and compared with log-rank test. Results: 206 patients were identified from 5 institutions. Mean age at treatment was 61 years (range 28 – 85). 55% presented with visceral disease. Lines at where palbociclib + fulvestrant treatment was administered were as follows: 1% 1st line, 8.3% 2nd line, 19.4% 3rd line, 13.6% 4th line, 10.2% 5th lignes and the remaining 47.6% had received ≥6 lines (median: 5 lines, range 1 to 15). A total of 48% patients had previously been treated with fulvestrant. In a subsample of patient where the information was available (n=146), 67.8% patients had received everolimus in combination with endocrine therapy before palbociclib administration. A total of 77 patients were still on treatment. Median PFS on fulvestrant-palbociclib treatment at the date of data cut-off was of 5.46 months (95% CI; 4.6 to 6.6 months). In a univariate analysis, there were no significant differences in median PFS for patients treated or not with previous fulvestrant, suggesting a potential effect of palbociclib to recover sensitivity to fulvestrant (4.7 months for previous fulvestrant treatment [95% CI 4.07 - 6.3 months] vs 6.1 months for no previous fulvestrant [95% CI; 6.3 - 8.02 months], p=0.3559). Similarly, in the subsample of n=146 patients where information about previous everolimus treatment was available at data cut-off, benefit from palbociclib-fulvestrant was not affected by previous everolimus treatment (median PFS 4.8 months for previously treated [95% CI; 4.01 -7.8 months] vs 5.4 months for the untreated everolimus group [95% CI; 4.07 - 9.59 months], p=0.374). Conclusions: Fulvestrant-palbociclib in the real life is associated with a median PFS of 5.5 months, which is below the results provided in the PALOMA-3 trial, reflecting a much more advanced population. Importantly, neither previous everolimus treatment nor fulvestrant therapy affected benefit from fulvestrant-palbociclib in this population in univariate analyses suggesting a potential recovery of fulvestrant sensitivity with CDK4/6 inhibition. Results from multivariate analyses and more detailed information about patients' characteristics and benefit from previous therapies will be provided. Citation Format: Arnedos M, Rusquec P, Morelle M, Lebreton C, Jacquet E, Emile G, Aires J, Debled M, Frenel J-S, Augereau P, Cheaib B, Levy C, Bachelot T. Benefit from palbociclib and fulvestrant based on previous fulvestrant and/or everolimus treatment. Based on a cohort of over 200 patients treated in a French compassionate program [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P5-21-11.

Patterns of treatment and outcome of palbociclib plus endocrine therapy in hormone receptor-positive/HER2 receptor-negative metastatic breast cancer: a real-world multicentre Italian study

“…In two previous compassionate use programmes, no differences in median PFS were observed in patients receiving palbociclib following fulvestrant and/or everolimus. 45,46 This is consistent with our results: in the subgroup analysis, 32.4% of patients pretreated with everolimus/exemestane and 35.5% of patients previously treated with fulvestrant obtained an objective response, reinforcing recent suggestions that palbociclib could reverse the acquired resistance to ET. 9,47,48 A more recent trial on 60 everolimus-pretreated patients reported a median PFS of 5.8 months in the whole population and 6.4 months in 48% of patients also receiving fulvestrant as previous treatment line.…”

CDK4/6 Inhibitors in HR+/HER2- Advanced/metastatic Breast Cancer: A Systematic Literature Review of Real-World Evidence Studies

“…The range of median PFS for palbociclib plus fulvestrant across all lines of treatment in RWE studies was 5.46-13.3 months, which was overall comparable to 11.2 months observed in the PALOMA-3 clinical trial [19]. The lower end of this range (5.46 months) was also from a study that included heavily pretreated patients [36]. However, follow-up period for most studies remained low.…”

Palbociclib plus endocrine therapy in HER2 negative, hormonal receptor‐positive, advanced breast cancer: A real‐world experience

“…Almost a half of them received more than 6 lines, 48% of these patients had previously been treated with fulvestrant and 67.8% with everolimus in combination with ET. The median PFS of patients treated with fulvestrant and palbociclib was 5.46 months, with no significant differences between patients pretreated with fulvestrant or everolimus in univariate analysis (Arnedos et al, ). Within a compassionate use program, another single‐centre retrospective analysis of 34 heavily pretreated patients showed a disease control rate of 52.9% at Week 12 and 24.4 at Week 24, and a PFS of 3.1 months, with no significant difference between everolimus‐pretreated (3.5 months) and everolimus‐naïve patients (2.7 months; Maurer et al, ).…”