breast cancer

Triplet Therapy With Palbociclib, Taselisib, And Fulvestrant In PIK3CA -Mutant Breast Cancer And Doublet Palbociclib And Taselisib And Pathway Mutant Solid Cancers

In a recent article published in the Journal Cancer Discovery, January 2021, authors investigated the triplet (Palbociclib, Taselisib, And Fulvestrant ) and doublet combination (Palbociclib and Taselisib) therapy in a variety both breast cancer and other solid tumors with mutated PIK3CA signaling pathways.  The underlying theory is that cyclin dependent kinase 4/6 and PI3K inhibitors synergize in patients with estrogen receptor positive HER-2/neu negative PIK3CA mutated breast cancer (as well as other tumors).  

A phase 1B clinical trial was developed, to determine the safety and efficacy of doublet palbociclib plus the selective PI3K inhibitor taselisib with or without fulvestrant in 25 patients with advanced solid tumors.  Breast cancer patients were given the triplet therapy while breast cancer patients were given the doublet. 

PIK3CA mutation was a necessary inclusion criteria. The triplet therapy response rate in breast cancer patients was 37.5%, 95% confidence interval 18.8–59.4.  Durable disease control was seen in patients with breast cancer and other solid tumors.  Both combinations were reported to be well-tolerated.  A high baseline cyclin D1 expression was associated with shorter progression free survival in the triplet group, hazard ratio 4.2 with a 95% confidence interval 1.3–13.1, p = 0.02 for progression free survival.  

Early circulating tumor DNA dynamics demonstrated high on-treatment circulating tumor DNA association with shorter progression free survival, hazard ratio 5.2, 95% confidence interval 1.4–19.4, p = 0.04.  The authors noted that longitudinally collected plasma circulating tumor DNA sequencing offered evolution of the tumor genome during triplet therapy.  

The authors concluded that patients with estrogen receptor positive HER-2/neu negative PIK3CA mutated advanced breast cancer who were heavily treated, derived clinical benefit from the triplet combination of palbociclib, taselisib, and fulvestrant.  They also noted that triple negative breast cancer patients derived some clinical benefit as well with doublet therapy.