Practice-changing endocrine trials shed light on breast cancer treatment, management

There are several such biomarkers under investigation, but they need validation and testing in large scale clinical trials before they find their way into day-to-practice, said Dr Bardia, who was not involved in the studies.

— Neil Osterweil

CTCs help predict breast cancer outcomes in neoadjuvant setting

Key clinical point CTCs are a useful prognostic biomarker in early breast cancer patients treated with neoadjuvant chemotherapy. Major finding OS was associated with the presence of at least 2 CTCs at baseline (HR, 2.6 for 2 CTCs; 3.84 for 3-4 CTCs; and 6.25 for 5 or more CTCs). Data source Meta-analysis of data for 2156 patients. Disclosures Supported by a research grant from Janssen Diagnostics. Dr Bidard reported having no disclosures.

Circulating tumor cells (CTCs) are a useful prognostic biomarker in early breast cancer patients treated with neoadjuvant chemotherapy, according to findings from an international meta-analysis of individual patient data. The cells, which can be measured using a Food and Drug Administration-approved assay, are known to seed distant metastases and to be prognostic before and during therapy for patients with metastatic breast cancer, and prognostic before adjuvant therapy for patients with nonmetastatic breast cancer.

However, findings in the neoadjuvant setting have been varied, Francois-Clement Bidard, MD, of Institut Curie, Paris, reported at the symposium.

In the IMENEO study, CTCs were useful, independent of pathologic complete response, for predicting overall survival and distant disease-free survival in the neoadjuvant setting. In addition, the findings showed for the first time that CTCs also predict locoregional relapse-free survival. Based on an analysis of data from 2156 patients from 21 studies at 16 centers in 10 countries, the CTC positivity rates using thresholds of one or more, two or more, and five or more, respectively, were 25%, 13%, and 6% in 1574 patients tested at baseline; 17%, 6%, and 3% in 290 tested after neoadjuvant chemotherapy; 15%, 5%, and 1% in 1,200 tested before surgery; and 11%, 4%, and 1% in 285 tested after surgery, Dr Bidard said.

Prior to neoadjuvant chemotherapy, at least one CTC was found in 19%, 22%, 24%, 29%, and 41% of cT1, T2, T3, T4a-c, and T4d breast cancers, respectively, and this was marginally associated with hormone receptor negativity, he said, noting that later CTC detection rates were not associated with any patient baseline characteristics. Nearly one in four patients (24%) achieved pathologic complete response, but this was not associated at any time point with CTC count.

For the primary study endpoint of overall survival, a significant association was found with the presence of at least two CTCs at baseline (hazard ratio, 2.6 for two CTCs; 3.84 for three to four CTCs; and 6.25 for five or more CTCs). Similar associations were found for distant disease-free survival (hazard ratios, 2.4, 3.4, and 5.0, respectively) and for locoregional relapse-free interval with two CTCs and five or more CTCs (hazard ratios, 2.4 and 4.2, respectively).

Similar results were found using later time points, such as after the start of neoadjuvant chemotherapy or before surgery, he said.

On multivariate analysis, baseline CTC detection using any of the thresholds remained an independent predictor of overall and distant disease-free survival and locoregional relapse-free interval when considered together with pathologic complete response, cT, cN, and tumor subtype, suggesting that CTC measurement adds value to comprehensive prognostic models. That is, they complement rather than duplicate usual prognostic factors and pathologic complete response rates to better predict outcomes in patients with early breast cancer in the neoadjuvant setting, Dr Bidard said.

— Sharon Worcester

PIK3 inhibitor gives slight PFS edge at high cost for advanced breast cancer

Key clinical point The PI3K inhibitor buparlisib plus fulvestrant slightly prolonged progression-free survival of HR+/HER2- breast cancer pretreated with an aromatase inhibitor and mTOR inhibitor. Major finding The combination met its primary endpoint of better PFS than fulvestrant/placebo, but with high liver toxicity and mood disorders. Data source Randomized phase 3 trial of 432 women with HR-positive, HER2-negative, AI-pretreated breast cancer that progressed on or after mTOR inhibitor therapy. Disclosures Novartis sponsored the study. Dr Di Leo disclosed consulting and lecture fees from the company, and Dr O’Regan disclosed contracted research support. Dr Arteaga reported no disclosures relevant to the study.

A combination of a PI3K inhibitor and selective estrogen receptor down-regulator (SERD) met its primary endpoint of 2.1 months better progression-free survival (PFS) in postmenopausal women with locally advanced or metastatic breast cancer who were quickly running out of other treatment options, but the small gain in PFS came at a very high price in terms of toxicities, including mood disorders that may have led to patient suicide attempts, according to investigators.