Abstract

SummaryThis article reviews the clinically most relevant presentations at the American Society of Clinical Oncology (ASCO) annual meeting 2018 on the topic of metastatic breast cancer. In the randomized placebo-controlled phase 3 trial MONALEESA-3, testing ribociclib vs. placebo in combination with fulvestrant in postmenopausal women or men with hormone receptor-positive (HR+) and HER2-negative (HER2−) advanced breast cancer (ABC), an increase of median progression-free survival (PFS) from 12.8 months to 20.5 months by the addition of the CDK4/6 inhibitor was reported (HR 0.59; P > 0.01). Taselisib, an alpha specific PI3K inhibitor, was tested in combination with fulvestrant in pretreated HR+/HER2− ABC patients with PIK3CA mutations in the placebo-controlled phase 3 trial SANDPIPER. PFS was significantly longer (7.4 months vs 5.4 months; HR 0.70, P < 0.01) but severe adverse events were more frequent (32% and 9%) in the taselisib group. In triple-negative breast cancer, the AKT inhibitor capivasertib (AZD5363) was combined with paclitaxel as first-line treatment in the placebo-controlled phase 2 trial PAKT. In patients with altered PIK3CA, AKT1 or PTEN, median PFS increased from 3.7 months to 9.3 months (HR 0.30; two-sided P = 0.01). No treatment effect was shown in the non-altered group. The most common adverse events attributed to capivasertib were diarrhea, fatigue and stomatitis. Results of two phase I trials of trastuzumab antibody-drug conjugates (ADCs) indicated HER2 as a non-oncogenic surface target in breast cancer patients expressing HER2.

Highlights

  • At this year’s American Society of Clinical Oncology (ASCO) meeting Dennis Slamon presented the primary results of the randomized phase 3 trial of the CDK4/6 inhibitor ribociclib or placebo in combination with fulvestrant in postmenopausal women or men with hormone receptor-positive (HR+) and HER2-negative advanced breast cancer (ABC) [1, 2]

  • Ribociclib combined with fulvestrant may be a new first- or second-line treatment option for postmenopausal women with HR+/HER2– advanced breast cancer

  • In the randomized phase 3 trial PHEREXA the addition of pertuzumab to trastuzumab plus capecitabine was investigated in HER2-positive metastatic breast cancer patients progressing during or after a trastuzumab-based therapy

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Summary

Introduction

At this year’s ASCO meeting Dennis Slamon presented the primary results of the randomized phase 3 trial of the CDK4/6 inhibitor ribociclib or placebo in combination with fulvestrant in postmenopausal women or men with hormone receptor-positive (HR+) and HER2-negative advanced breast cancer (ABC) [1, 2]. In this randomized phase 3 trial palbociclib and fulvestrant was compared with placebo plus fulvestrant in pretreated postmenopausal women with HR+/HER2- advanced breast cancer.

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