Gilmored.

Top Line: Pathologic complete response (pCR) is the ultimate goal of any neoadjuvant therapy regimen for breast cancer.

The Study: It is the outcome measure that is associated with improvements in tumor control and survival outcomes, not to mention it’s associated with getting an FDA indication. Hormone receptor(+) breast cancers, while having more favorable overall outcomes, typically have less favorable responses to neoadjuvant therapy. The PI3K pathway is a mechanism of endocrine therapy resistance in more advanced hormone receptor(+) breast cancers, so in the LORELEI trial, the PI3K-inhibitor taselisib was added to neoadjuvant letrozole in postmenopausal women with stage I-III breast cancer. While all patients had testing for PIK3CA mutation, it wasn’t required for entry. They received daily letrozole and 5 days-on, 2 days-off taselisib for 16 weeks prior to surgery. Primary endpoints were 1) objective response on MRI and 2) complete response on final pathology. While objective response was significantly higher with taselisib (39→ 50%), the pCR rate was improved from a measly 1% to a still measly 2%. Plus serious adverse infections and GI events were more common with taselisib. While it would be surprising if such a poor rate of pCR translated into a clinical indication, it's not unheard of.

TBL: The PI3K inhibitor, taselisib, produces objective responses, but not pathologic complete responses, in the neoadjuvant setting for early stage breast cancer. | Saura, Lancet Oncol 2019