Palbociclib in Breast Cancer
|Target||Development Name||Generic Name||Trade Name||Status|
|CDK4/6||PD0332991||palbociclib||Ibrance||FDA approved in combination with letrozole for ER-positive breast cancera|
a ER-positive, HER2-negative first-line metastatic breast cancer patients treated with palbociclib in combination with the aromatase inhibitor letrozole demonstrated an improvement in median progression-free survival compared with letrozole alone in a randomized phase 2 trial (Table 1; PALOMA-1; Finn et al. 2015). Based on the outcomes from this trial, the combination of palbociclib and letrozole received accelerated FDA approval for ER-positive, HER2-negative first-line metastatic breast cancer in 2015 (FDA 2015). The phase 3 trial of this combination is still ongoing.
A phase III trial evaluating palbociclib in combination with fulvestrant in metastatic ER-positive, HER2-negative breast cancer following disease progression during or after endocrine therapy showed improved progression-free survival relative to patients treated with placebo plus fulvestrant (Table 1; PALOMA-3; Turner et al. 2015). The trial was stopped early due to efficacy. In a subgroup analysis, premenopausal/perimenopausal patients with ovarian suppression demonstrated equivalent efficacy benefit with combination therapy as postmenopausal breast cancer patients (Turner et al. 2015).
In a preliminary report of a phase 1 study of palbociclib in combination with paclitaxel in RB+ third-line metastatic breast cancer (any ER status), patients experienced a 73% clinical benefit rate treated with combination therapy (Table 1; Clark et al. 2014).
RB1-positive metastatic breast cancer patients treated with single-agent palbociclib demonstrated a 19% clinical benefit rate and a median progression-free survival of 3.7 months. In a hormone receptor positive patient subset with greater than or equal to two prior lines of hormone therapy, the clinical benefit rate was 29% and the median progression-free survival was 5.0 months (Table 1; DeMichele et al. 2014).
Table 1. Reported Trials with Palbociclib in Breast Cancer.
|Reference||Study Type / Phase||Therapeutic setting||Treatment Agent||Mutation Status / Group||# Pts in Study||RR||PFS (months)||OS (months)|
|Turner et al. 2015 (PALOMA-3)||Phase 3||≥1st (no limit to prior therapies) metastatic or advanced breast cancer||palbociclib + fulvestrant||HR+||347||10.4%||9.2|
|placebo + fulvestrant||174||6.3%||3.8|
|Finn et al. 2015 (PALOMA-1; TRIO-18)||Phase 2||1st line
metastatic breast cancer
|letrozole||ER+ / HER2– (cohort 1+2)||81||27%||10.2||33.3|
|ER+ / HER2– (cohort 1)||32||5.7|
|ER+ / HER2– / CCND1+ or p16+ (cohort 2)||49||11.1|
|letrozole + palbociclib||ER+ / HER2–(cohort 1+2)||84||43%||20.2||37.5|
|ER+ / HER2– (cohort 1)||34||26.1|
|ER+ / HER2– / CCND1+ or p16+ (cohort 2)||50||18.1|
|DeMichele et al. 2014||Phase 2||≥1st (no limit to prior therapies)
metastatic breast cancer
|HR+ / RB1+ subset||33||5.1|
|≥2 prior lines of hormone therapy||HR+ / RB1+ subset||24||5.0|
|Clark et al. 2014||Phase 1||≥3rd line metastatic breast cancer||palbociclib + paclitaxel||RB1+||15||40%|
NOTE: CR = complete response; ER = estrogen receptor; OS = overall survival; PFS = progression-free survival; PR = partial response; Pts = patients; RR = response rate (CR + PR); RB1 = retinoblastoma.
Table 2. Ongoing and Recruiting Clinical Investigation with Palbociclib in Breast Cancer.
|Study Type / Phase / ID||Therapeutic setting||Prior therapy requirement||Treatment Agent||Mutation Status / Group||# Pts in Study||Study Start Date|
|Phase 1b (NCT01976169)||2nd line or greater, recurrent or metastatic breast cancer||Prior trastuzumab or HER2 targeted therapies required||palbociclib + Trastuzumab-DM1||HER2+
|Phase 3 (PEARL, NCT02028507)||Any line, locally advanced or metastatic breast cancer||Recurrence during or within 12 months of adjuvant letrozole or anastrozole or during or within 1 month of letrozole or anastrozole for metastatic disease||palbociclib + exemestane||ER+ and/or PR+
|Phase 3 (PALOMA-2, NCT01740427)||1st line||No prior systemic anti-cancer therapy for advanced ER+ disease||palbociclib + letrozole||ER+
|placebo + letrozole|
|Phase 3 (PENELOPE-B, NCT01864746)||Early breast cancer at high risk of relapse after showing less than pathological complete response to neoadjuvant taxane-containing chemotherapy||Prior neoadjuvant chemotherapy including taxane of at least 16 weeks||palbociclib + standard anti-hormonal therapy||ER+ and/or PR+
|Placebo + standard anti-hormonal therapy|
|Phase 2 (NCT02040857)||Adjuvant setting, breast cancer||One month of adjuvant tamoxifen or aromatase inhibitor; at least two more years of adjuvant therapy planned||palbociclib + tamoxifen or letrozole or anastrozole or exemestane||ER+ and/or PR+
|Phase 2 (NCT01723774)||Neoadjuvant setting||palbociclib + anastrozole or anastrozole + goserelin||ER+ and/or PR+
PIK3CA mutation cohort
Suggested Citation: Balko, J., I. Mayer, M. Levy, C. Arteaga. 2015. Palbociclib in Breast Cancer. My Cancer Genome http://www.padiracinnovation.org/content/molecular-medicine/palbociclib-breast-cancer/ (Updated June 17).
Last Updated: July 24, 2015