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
palbociclib RB1+ 37   3.7  
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+
17 January 2014
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+
348 March 2014
Phase 3 (PALOMA-2, NCT01740427) 1st line No prior systemic anti-cancer therapy for advanced ER+ disease palbociclib + letrozole ER+
650 February 2013
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+
800 November 2013
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+
120 January 2014
Phase 2 (NCT01723774) Neoadjuvant setting   palbociclib + anastrozole or anastrozole + goserelin ER+ and/or PR+
PIK3CA mutation cohort
29 June 2013

NOTE: ER = estrogen receptor; HER2 = human epidermal growth factor receptor 2; PR = progesterone receptor; RB1 = retinoblastoma.

Contributors: Justin M. Balko, Pharm. D., Ph.D., Ingrid A. Mayer, M.D., M.S.C.I., Mia Levy, M.D., Ph.D., Carlos L. Arteaga, M.D.

Suggested Citation: Balko, J., I. Mayer, M. Levy, C. Arteaga. 2015. Palbociclib in Breast Cancer. My Cancer Genome (Updated June 17).

Last Updated: July 24, 2015

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