Shedding light on endocrine therapy sequencing for advanced breast cancer

The optimal sequencing of treatment for hormone therapy-naïve, post-menopausal women with hormone receptor-positive advanced breast cancer needs to be confirmed

  • Date: 09 Oct 2016
Breast_Cancer_Turner

Nicholas Turner: Royal Marsden NHS Foundation Trust and Institute of Cancer Research, London, UK

The optimal sequencing of treatment for hormone therapy-naïve, post-menopausal women with hormone receptor-positive advanced breast cancer needs to be confirmed, particularly in view of practice-changing Late-Breaking Abstracts presented yesterday with results from two randomised phase III trials.

In the first presentation of results from the large MONALEESA-2 trial in 668 patients with untreated hormone receptor-positive/HER2-negative disease, Professor Gabriel Hortobagyi from the University of Texas MD Anderson Cancer Center, Houston, Texas, USA, reported progression-free survival (PFS) benefit with the addition of the selective CDK4/6 inhibitor ribociclib to letrozole (Abstract LBA1_PR). In a pre-planned interim analysis (after 243 PFS events) the hazard ratio (HR) was 0.556 (95% confidence interval [CI] 0.429–0.720; p=0.00000329) in favour of letrozole plus ribociclib. Ribociclib increased the rate of grade 3–4 neutropenia (59% versus 1%) and leukopenia (21% versus 1%) compared with letrozole alone.

The CDK4/6 inhibitors, including palbociclib (approved by the US FDA) and abemaciclib, are changing the breast cancer treatment landscape. “Testing combinations of ribociclib with other inhibitors of various signalling pathways might lead to additional progress in the management of several subtypes of breast cancer,” suggested Professor Hortobagyi.  According to results from the large FALCON trial presented earlier in the day by Dr Matthew Ellis from Baylor College of Medicine, Houston, Texas, USA, fulvestrant is significantly more effective than anastrozole in hormone treatment-naïve patients with oestrogen receptor-positive and/or progesterone receptor-positive, locally advanced or metastatic breast disease (Abstract LBA14_PR). Among 462 patients randomised, fulvestrant significantly reduced the chance of progression compared with anastrozole (HR 0.797; 95% CI 0.637–0.999; p=0.0486), with median PFS times of 16.6 months and 13.8 months, respectively.

No significant difference in overall survival was observed. Health-related quality of life was similar in both arms.

The results of these two studies are practice changing, yet they propose two different standards for the initial treatment of hormone therapy-naïve disease, with fulvestrant or with aromatase inhibitor-CDK4/6 inhibitor combinations. Further studies are going to be required to establish the optimal sequence of these agents, and help clinicians select the most appropriate therapy. 

This article appeared in the Sunday edition of the Daily Reporter