The safety and efficacy of palbociclib in older patients with advanced breast cancer in a real-world setting

Abstract

Aims: Palbociclib has been approved in combination with endocrine therapy (ET) for hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer (ABC), regardless of age. Even though ABC is one of the most prevalent cancers in older patients, very few patients ≥ 65 years old were included in pivotal trials. Therefore, the current study evaluated the safety and efficacy of palbociclib in “real-world” routine treatment of unselected older patients with HR+/HER2- ABC. Methods: Data were collected on patients > 70 years old who were treated with palbociclib plus ET for HR+/HER2- ABC in our institution. We analyzed safety data (CTCAE v4.0 criteria) and outcomes, such as progression-free survival (PFS) and overall survival (OS), as well as any associations between main geriatric characteristics and our results. Furthermore, we assessed safety at a national level by analyzing all palbociclib-related adverse events (AEs) reported in the French Pharmacovigilance Database (FPVD) during the same period. Results: From February 2016 to July 2019, 52 patients were identified with a median age of 80.9 years, of whom 88% presented an AE. The most common grade 3-4 AE was neutropenia (64%). Median PFS and OS were nine months and not reached, respectively. The FPVD reports 227 cases of palbociclib-related AEs, with older and younger patients sharing similar characteristics. Conclusion: Palbociclib is well tolerated in older patients with efficacy comparable to that in younger patients. However, the addition of palbociclib to ET should be evaluated individually in this older and frailer subgroup.

Palbociclib in Older Patients with Advanced/Metastatic Breast Cancer: A Systematic Review

“…Most of the RWE studies were retrospective ( n = 32) [ 30 – 59 ]; three studies were prospective [ 60 – 65 ], and two were ambispective (retrospective and prospective) studies [ 66 , 67 ]. Three retrospective studies using data from the Flatiron Health longitudinal database had different study time frames and populations (in terms of patient age); however, there remains a possibility of patient overlap across studies [ 35 , 37 , 52 ].…”

“…Three retrospective studies using data from the Flatiron Health longitudinal database had different study time frames and populations (in terms of patient age); however, there remains a possibility of patient overlap across studies [ 35 , 37 , 52 ]. Older patients were defined as ≥ 60 years of age in one study [ 40 ], ≥ 65 years in 21 studies [ 30 , 32 , 34 , 36 – 39 , 42 , 43 , 45 , 46 , 49 , 50 , 52 , 53 , 56 – 58 , 64 , 65 , 68 ], ≥ 70 years in 11 studies [ 31 , 44 , 47 , 48 , 54 , 55 , 59 – 63 , 66 , 67 ], and ≥ 75 years in four studies [ 33 , 35 , 41 , 51 ]. Three studies evaluated CDK 4/6 inhibitors as a class; however, ≥ 80% of the patients received palbociclib as the CDK 4/6 inhibitor [ 43 , 58 , 67 ].…”

“…Of the included 37 RWE studies, seven included only older patients [ 37 , 41 , 43 , 59 – 63 ]. Among RWE studies including both younger and older patients, six studies provided data on the proportion of patients aged ≥ 75 years (31% [1960 of 6380]) [ 36 , 37 , 45 , 46 , 51 , 52 ].…”

“…Of the 26 RWE studies (nine in first-line setting; 15 regardless of line of therapy; line of therapy not specified in two studies) that reported PFS data, 20 studies compared results between older and younger patients (Table 1 ). In 16 studies, there was no significant difference in real-world progression-free survival (rwPFS) between younger and older patients who received treatment with palbociclib [ 34 , 38 , 39 , 46 – 49 , 51 – 53 , 55 , 56 , 58 , 59 , 65 , 67 , 68 ]. In three studies, rwPFS benefit was comparable between younger and older patients; however, no test for significance was conducted [ 45 , 50 , 66 ].…”

“…In one study, rwPFS rate at 12 months was significantly longer in patients ≥ 65 years of age versus patients aged < 65 years [ 64 ]. Six studies included only older patients [ 33 , 35 , 37 , 41 , 59 , 60 ]; in one study using multivariable regression, age (as a continuous variable) was not a significant predictor of rwPFS [ 41 ]. In all three RWE studies with a control arm (two of these three studies included only older patients [ 35 , 37 ]), older patients treated with palbociclib had significantly longer rwPFS compared with control treatment [ 35 , 37 , 52 ].…”