Primary results of LORELEI study presented at ESMO 2017 Congress
Primary results of LORELEI study presented at ESMO 2017 Congress
(European Society for Medical Oncology, Madrid, 08/09/2017)
08 Sep 2017
The LORELEI study shows taselisib and letrozole given prior to surgery significantly increases objective response rates compared to letrozole alone in women with ER-positive, HER2-negative early breast cancer
Brussels, 8 September 2017.- The Breast International Group (BIG), the Austrian Breast & Colorectal Cancer Study Group (ABCSG), and the SOLTI Breast Cancer Research Group today announced positive results from the randomised phase II LORELEI study. The study, sponsored by Genentech, a member of the Roche group, was designed to evaluate taselisib plus letrozole versus placebo plus letrozole given prior to surgery (neoadjuvant treatment) in postmenopausal women with ER-positive/HER2-negative early-stage breast cancer. LORELEI has met its primary objective and showed that the addition of taselisib increased the objective response rate (ORR) from 38% to 56.2% in patients with PIK3CA mutation and from 39.3% to 50% across all patients in the study. No significant difference was observed for pathologic complete response (pCR) rate with the addition of taselisib to letrozole. LORELEI is the first randomised study testing the addition of a selective PI3K inhibitor in combination with endocrine therapy and utilising centrally assessed MRI to evaluate tumour response in a neoadjuvant endocrine trial for patients with early breast cancer. The safety profile was manageable.
Taselisib is an oral selective PI3-kinase (PI3K) inhibitor with enhanced activity against PIK3CA mutant cancer cells via a novel mechanism of action. PI3K pathway is critical for cell-cycle modulation, cell growth, metabolism, motility, and survival. PIK3CA mutation, as one of the major mechanisms leading to PI3K pathway activation, is found in approximately 40-45% of ER-positive breast cancers. Additionally, preclinical evidence suggests that elevated PI3K pathway activity is associated with resistance to endocrine therapy. Thus, it is believed that blocking PI3K signalling may stop or slow the growth of certain breast cancers and potentially other types of tumours. Clinical data from early trials have demonstrated anti-tumour activity in patients with PIK3CA mutant breast cancer treated with taselisib either as a single agent or combined with endocrine therapy.
Results of the LORELEI primary analysis were presented in an oral session today at the European Society for Medical Oncology (ESMO) Congress in Madrid (Spain) by Cristina Saura, M.D., PhD, study primary investigator (Abstract #LBA10), and is featured in ESMO’s official press programme.
Dr. Saura (Vall d’Hebrón University Hospital and Vall d’Hebrón Institut of Oncology Barcelona, Spain) added: “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. The study incorporates an extensive biomarker programme to guide further clinical development, both in the early and metastatic breast cancer settings. This is an important clinical trial, and to accrue patients successfully, the support of patients and researchers internationally was absolutely essential. BIG, together with ABCSG and SOLTI, have been instrumental in facilitating this international collaboration. The results of the LORELEI study will help guide further clinical research in ER-positive/HER2-negative breast cancer.”
About the LORELEI study
LORELEI: a phase II randomised, double-blind study of neoadjuvant letrozole plus taselisib versus letrozole plus placebo in postmenopausal women with ER-positive/HER2-negative early-stage breast cancer
- Co-primary endpoints: ORR (Objective Response Rate) by centrally assessed breast MRI (via modified RECIST criteria) and pathologic complete response (pCR) rate in breast and axilla at time of surgery, in all randomised patients and in patients with PIK3CA mutant tumours.
- Key secondary endpoints: ORR (Objective Response Rate) by centrally-assessed MRI in patients with PIK3CA wild-type tumours, pCR rate in patients with PIK3CA wild-type tumours, and safety overall.
Study methods: 334 postmenopausal women with newly diagnosed ER-positive/HER2-negative-, untreated, Stage I-III operable breast cancer and evaluable tumour tissue for PIK3CA genotyping were randomised (1:1) in 85 sites across 22 countries to receive letrozole (2.5 mg daily) with either taselisib (4 mg on a 5 days on/ 2 days off schedule) or placebo for 16 weeks, followed by surgery. The co-primary endpoints were overall objective response rate (ORR) by centrally assessed breast magnetic resonance imaging (MRI) and pathologic complete response (pCR) rate in breast and axilla at surgery, in all randomised patients and in patients with PIK3CA mutant tumours. One planned interim safety analysis and two safety monitoring meetings have been conducted by an Independent Data Monitoring Committee (IDMC), with the recommendation to continue the trial without modifications.
- Collaborative study partners: the Breast International Group (BIG), the Austrian Breast & Colorectal Cancer Study Group (ABCSG), and the SOLTI Breast Cancer Research Group
- Pharmaceutical partner and sponsor: Genentech, a member of the Roche group, and study sponsor, provided funding for this study
- Groups enrolling patients: ABCSG (Austrian Breast & Colorectal Cancer Study Group), ANZBCTG (Australia and New Zealand Breast Cancer Trials Group), EORTC (European Organisation for Research and Treatment of Cancer), GECOPERU (Grupo de Estudios Clínicos Oncológicos Peruano), GOIRC (Gruppo Oncologico Italiano di Ricerca Clinica - Italian Oncology Group of Clinical Research), IBCSG (International Breast Cancer Study Group), LACOG (Latin American Cooperative Oncology Group), and SOLTI (Spanish Breast Cancer Research Group)
- Sites: 85 sites worldwide in 22 countries, including 8 BIG Groups, are participating in the study
- Clinical trial information: NCT02273973
About ER-positive/HER2-negative Breast Cancer
ER-positive/HER2-negative breast cancer is the most common subtype of this disease, characterised by expression of ER (oestrogen receptor) and lack of expression of HER2 (human epidermal growth factor receptor 2). Tumours that are ER-positive are much more likely to respond to treatments that block oestrogen. The most common treatment for ER-positive and HER2-negative breast cancer is hormone blocking therapy. The prognosis for patients with ER-positive and HER2-negative breast cancer depends on how advanced the cancer was when it was detected. Prognosis is also influenced by the size of the tumour and if the cancer has spread to other organs. Despite the favourable prognosis of patients with early stage ER-positive, HER2-negative breast cancer receiving endocrine therapy, a substantial proportion of them will experience recurrence of their disease. Resistance to endocrine treatment can be fuelled by several alternative oncogenic signalling pathways, with an abundance of evidence identifying activation of PI3K signalling as mediator of such resistance.