LORELEI Study at ESMO 2017

Intro text: 

Letrozole combined with taselisib shows better outcome for postmenopausal women with early stage breast cancer

The primary results of LORELEI (BIG 3-13), an international two-arm, randomised, phase II trial, indicate that taselisib and letrozole given prior to surgery significantly increases objective response rates (ORR) compared to letrozole alone in women with ER-positive, HER-negative early breast cancer.

As announced earlier today, LORELEI has met its primary objective and showed that the addition of the PI3K inhibitor taselisib to the standard neoadjuvant endocrine treatment increased the objective response rate (ORR) from 38% to 56.2% in patients with PIK3CA mutations and from 39.3% to 50% across all patients in the study. 
No significant difference in the pathologic complete response (pCR) was observed between the two arms of the study (letrozole + taselisib vs letrozole alone). Tumour response was evaluated by using centrally assessed breast MRI. The patient safety profile was reported to be manageable.

The study results will be presented by Dr Cristina Saura, study primary investigator during an oral session today at 2 PM at the 2017 ESMO Congress in Madrid, Spain.

Overcoming resistance to endocrine treatment
In ER+ breast cancer, patients can become resistant to endocrine treatments like letrozole, and this appears to be related to the activation of the PI3K pathway. Therefore, it is hypothesised that blocking the action of this pathway through a PI3K inhibitor given together with the endocrine treatment could be more effective than the standard treatment alone.

LORELEI was designed to determine if combining the PI3K inhibitor taselisib (GDC-0032) with letrozole in the neoadjuvant treatment of postmenopausal patients with ER+/HER- untreated, operable early breast cancer is better than giving letrozole alone. 

Scientists leading this research want to better understand not only how taselisib combined with letrozole works, but also whether there are factors that can predict whether a patient will be sensitive or resistant to the treatment, particularly what the role of the PIK3CA mutation is.

“The study incorporates an extensive biomarker programme to guide further clinical development, both in early and metastatic breast cancer settings”, says Dr Saura.

Dr Saura highlights that “the LORELEI study demonstrates the importance of industry-academic collaborations and their crucial role in finding treatments and improving care for people affected by breast cancer”.

She emphasises the key role played by BIG, ABCSG and SOLTI, which have been instrumental in facilitating international collaboration to set up and manage this trial.

International collaboration
The trial enrolled 334 patients from 85 sites across 22 countries. It is being conducted as a collaboration between the Breast International Group (BIG), the Austrian Breast & Colorectal Cancer Study Group (ABCSG), SOLTI and Genentech (Sponsor).


Read more about LORELEI