mTORn to pieces.
The Study: Don’t feel bad, that’s a tough one. The answer is more endocrine therapy. Typically with a different agent in combo with either a CDK4/6 inhibitor (category 1) or an mTOR inhibitor (i.e., drugs that end in -limus). The international BOLERO-6 trial enrolled 309 postmenopausal women with measurable ER(+), HER2(-) breast cancer refractory to letrozole or anastrozole. There was a 3-arm randomization:  capecitabine,  everolimus, or  everolimus + exemestane. Does something already feel off about this prospective breast cancer trial? At little over 100 patients per arm, this study was creatively designed notfor statistical analyses (as described in the “statistical analysis” section) but instead to provide “estimates’ of treatment effects. That's because the real rationale behind this Novartis-sponsored interim analysis was an FDA-mandate of data reporting post-approval of everolimus for this indication. Unfortunately for Novartis, capecitabine pulled off an unexpected numeric victory in the primary endpoint of “estimated” DFS when compared with everolimus + exemestane and everolimus alone: the median DFS times were 10, 8 and 7 months, respectively. Fortunately for Novartis, this wasn’t statistically significant.
Bottom Line: The authors conclude everolimus remains an important option for additional therapy for ER(+), HER2(-) breast cancer refractory to endocrine monotherapy...but CDK4/6-inhibition is probably more important. | Jerusalem, JAMA Oncol 2018