ESMO 2017: Adding Taselisib to Neoadjuvant Letrozole Improves Outcomes in Early Breast Cancer

Key Points

  • The study showed that objective response rate was better in patients who received taselisib compared to placebo (50% vs 39.3%), but there was no significant difference between the groups for pathologic complete response rate.
  • Among the 152 patients who had PIK3CA-mutant cancer cells detected at baseline, taselisib worked particularly well, with 56.2% showing an objective response rate compared to 38% of patients who received placebo.

Adding taselisib to letrozole before surgery significantly improved outcomes for patients with early breast cancer that was both estrogen receptor–positive and HER2-negative, according to results of the LORELEI trial, presented at the European Society for Medical Oncology (ESMO) 2017 Congress in Madrid (Abstract LBA10_PR).

“We were able to detect a reduction in tumor size after only 16 weeks of treatment, compared to patients who received letrozole plus placebo,” said study investigator Cristina Saura, MD, of Vall d’Hebron University Hospital in Barcelona. “Any decrease in tumor measurements is something positive for patients, because this means the drug has had activity against their tumor in a short period of time.”

LORELEI is the first randomized study to demonstrate a significant increase in objective response rate upon treatment with a PI3K inhibitor in this population of patients, noted the authors of the study, which was conducted in 85 sites across the world. Taselisib is an alpha-specific PI3K inhibitor.

“The alpha-specific story is important, because other PI3K inhibitors have had only a small effect, and the benefit-risk ratio was less favorable,” noted Sibylle Loibl, MD, PhD, Chair of the German Breast Group, who was not involved in the study but provided comment for ESMO. “In general it is believed that alpha-specific inhibitors will be more efficacious and less toxic than others.”

LORELI Findings

LORELEI included 334 postmenopausal patients with estrogen receptor–positive/HER2-negative, stage I–III, operable, early breast cancer. All of them had tissue analyzed for PIK3CA-mutant cancer cells and were randomized to receive letrozole plus either a placebo (n = 168) or taselisib (n = 166) for 16 weeks in order to shrink their tumor before surgery.

The study had two coprimary endpoints: objective response rate, which was assessed by measuring the tumor size with magnetic resonance imaging, and pathologic complete response rate.

The study showed that objective response rate was better in patients who received taselisib compared to placebo (50% vs 39.3%, odds ratio = 1.55, 95% confidence interval [CI] = 1.00–2.38, P = .049), but there was no significant difference between the groups for pathologic complete response rate.

Among the 152 patients who had PIK3CA-mutant cancer cells detected at baseline, taselisib worked particularly well, with 56.2% showing an objective response compared to 38% of patients who received placebo (odds ratio = 2.03, 95% CI = 1.06–3.88, P = .033).

“For me, the main message is that even though all patients seem to derive some benefit from taselisib, those who had this mutation seemed to derive more benefit,” said Dr. Saura.

Discontinuation and reduced dosing of taselisib occurred in 10.8% and 11.4% of patients, respectively. The most common serious (grade 3 and 4) adverse events associated with the drug included gastrointestinal disorders (7.8%); infections (4.8%); skin/subcutaneous tissue disorders (4.8%); vascular disorders (3.6%); and metabolism and nutrition disorders (3.6%), including hyperglycemia (1.2%).

Although there was one sudden death in the taselisib-treated group, the study investigators considered it unrelated to the drug.

Dr. Loibl concluded: “These are the first data indicating that the addition of an alpha-specific PI3K inhibitor might work in addition to an endocrine therapy in [estrogen receptor–positive/HER2-negative] breast cancer. More data from LORELEI, as well as data from the phase III studies in metastatic breast cancer, need to be [waited] for [in] evaluating the role of PIK3 kinase inhibitors in breast cancer.”

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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