eUpdate – Advanced Breast Cancer Treatment Recommendations

Published: 25 April 2017 Authors: ESMO Guidelines Committee

Clinical Practice Guidelines

This update refers to the 3rd ESO-ESMO International Consensus Guidelines For Advanced Breast Cancer (ABC 3). Cardoso F, Costa A, Senkus E, et al. Ann Oncol 2017; 28: 16-33.


ER-positive/HER-2 negative (luminal) ABC

Text update

Following the final publication of the PALOMA-2 results [1] and approval of palbociclib by the European Medicines Agency (EMA) in both first line [in combination with an aromatase inhibitor (AI)] and second line (in combination with fulvestrant), palbociclib is now available for many patients outside the United States and a few other selected countries.

Importantly, EMA approval includes the use of the drug in both pre- and postmenopausal patients, provided it is used in combination with a luteinising hormone-releasing hormone (LHRH) agonist.


The previously voted and approved ABC 3 recommendation regarding the use of palbociclib as 1st line therapy in combination with an AI is maintained as previously published, with the addition of the possibility of usage also in pre-menopausal patients:

The addition of the CDK 4/6 inhibitor palbociclib to an aromatase inhibitor, as first-line therapy, provided a significant improvement in PFS (10 months), with an acceptable toxicity profile and is, therefore, one of the preferred treatment options, where available, for pre-menopausal (in combination with a LHRH agonist) and post-menopausal patients (except patients relapsing < 12 months from the end of adjuvant AI). OS results are still awaited [IA].

In the absence of mature OS and quality of life data, the observed PFS benefit is associated with an ESMO Magnitude of Clinical Benefit Scale (ESMO-MCBS) score of 3.

ESMO-Magnitude of Clinical Benefit Scale (MCBS) table for new therapies/indications in ER-positive/HER-2 negative (luminal) ABC*

Therapy Disease setting Trial Control Absolute survival gain HR (95% CI) QoL/toxicity MCBS score**
Palbociclib plus letrozole Advanced disease in post-menopausal women not previously treated A Study of Palbociclib (PD-0332991) + Letrozole vs. Letrozole for 1st Line Treatment of Postmenopausal Women With ER+/HER2- Advanced Breast Cancer (PALOMA-2) [1]
Phase III
Letrozole plus placebo
Median PFS:
14.5 months
PFS gain:
10.3 months
PFS HR: 0.58 (0.46-0.72) Not yet available 3 (Form 2b, mature data on OS not available, data on QoL assessment not available)
Palbociclib plus fulvestrant Hormone-receptor-positive, HER-2-negative metastatic breast cancer previously treated with endocrine therapy Palbociclib (PD-0332991) Combined With Fulvestrant in Hormone Receptor+ HER2-Negative Metastatic Breast Cancer After Endocrine Failure (PALOMA-3) [2,3]
Phase III

Fulvestrant plus placebo

Median PFS: 4.6 months

PFS gain:
4.9 months
PFS HR: 0.46 (0.36-0.59)  QoL: delayed deterioration 4 (Form 2b, mature data on OS not available)

*EMA approvals from January 2016 to end January 2017.
** ESMO-MCBS version 1.0 [4]

ABC, advanced breast cancer; CI, confidence interval; EMA, European Medicines Agency; ER, oestrogen receptor; HER-2, human epidermal growth factor receptor 2; HR, hazard ratio; OS, overall survival; PFS, progression-free survival; QoL, quality of life


  1. Finn RS, Martin M, Rugo HS, et al. Palbociclib and Letrozole in Advanced Breast Cancer. N Engl J Med 2016; 375: 1925-1936.
  2. Cristofanilli M, Turner NC, Bondarenko I, et al. Fulvestrant plus palbociclib versus fulvestrant plus placebo for treatment of hormone-receptor-positive, HER2-negative metastatic breast cancer that progressed on previous endocrine therapy (PALOMA-3): final analysis of the multicentre, double-blind, phase 3 randomised controlled trial. Lancet Oncol 2016; 17: 425-439.
  3. Harbeck N, Iyer S, Turner N, et al. Quality of life with palbociclib plus fulvestrant in previously treated hormone receptor-positive, HER2-negative metastatic breast cancer: patient-reported outcomes from the PALOMA-3 trial. Ann Oncol 2016; 27: 1047-1054.
  4. Cherny NI, Sullivan R, Dafni U et al. A standardised, generic, validated approach to stratify the magnitude of clinical benefit that can be anticipated from anti-cancer therapies: the European Society for Medical Oncology Magnitude of Clinical Benefit Scale (ESMO-MCBS). Ann Oncol 2015; 26: 1547–1573.