Expert Point of View: Nadia Harbeck, MD, PhD, and Sibylle Loibl, MD


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Nadia Harbeck, MD, PhD

Nadia Harbeck, MD, PhD

NADIA HARBECK, MD, PhD, of the Breast Center at the University of Munich, Germany, said the findings of LORELEI are among a growing list of indications that “the future is bright for endocrine-based therapy.” 

Although the results were hypothesis-generating and not yet practice-changing, she pointed out that they are “the first clinical proof of efficacy of an alpha-specific PI3K [phosphoinositide 3-kinase] inhibitor in early breast cancer.” According to Dr. Harbeck, taselisib is not the first PI3K inhibitor to be evaluated, but being more selective, it may be the most tolerable so far. 

In the phase III BELLE-2 trial,1 the pan-PI3K inhibitor buparlisib, given with fulvestrant (Faslodex), produced clinically meaningful improvements in progression-free survival in patients with PIK3CA mutations, but this came at the price of substantial toxicity, she pointed out. Approximately 40% of patients receiving the combination had elevated liver enzymes, which were severe in about 25%. Hyperglycemia (43%), rash (32%), anxiety (22%), and depression (26%) were also seen more frequently in patients taking buparlisib. In contrast, taselisib was more tolerable, she pointed out.

Sibylle Loibl, MD

Sibylle Loibl, MD

“The results of the confirmatory phase III SANDPIPER trial of taselisib in metastatic breast cancer are eagerly awaited,” Dr. Harbeck commented. This was echoed by Sibylle Loibl, MD, Chair of the German Breast Group, who also sees more promise with taselisib than with other available agents in the class. 

“The alpha-specific story is important, because other PI3K inhibitors have had only a small effect, and the benefit-risk ratio was less favorable,” Dr. Loibl said. “In general, it is believed that alpha-specific inhibitors will be more efficacious and less toxic than others.” ■

DISCLOSURE: Drs. Harbeck and Loibl reported no conflicts of interest. 

REFERENCE 

1. Baselga J, Im S-A, Iwata H, et al: PIK3CA status in circulating tumor DNA predicts efficacy of buparlisib plus fulvestrant in postmenopausal women with endocrine-resistant HER+/HER2– advanced breast cancer: First results from the randomized, phase III BELLE-2 trial. 2015 San Antonio Breast Cancer Symposium. Abstract S6-01. Presented December 11, 2015.


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