Comparing letrozole and taselisib against letrozole and placebo before surgery in early stage breast cancer

This study aimed to investigate the combination of letrozole and taselisib as a neoadjuvant treatment (before surgery) in patients with hormone receptor-positive, HER2-negative, early stage breast cancer.  

This study concluded that this treatment increased objective response in these patients.  

Luminal breast cancer (LBC) is hormone-receptor-positive (estrogen-receptor and/or progesterone-receptor positive). Neoadjuvant treatment is that which is administered before the main treatment, commonly surgery to remove the tumor. Endocrine (hormone) therapy-based neoadjuvant treatment for luminal BC allows testing of new treatment combinations before surgery. 

BC can activate the PI3K pathway (PIK3CA mutant) to stop the endocrine therapy from working. Taselisib (GDC-0032) is a PI3K inhibitor. This means it blocks the PI3K pathway and allows endocrine therapy to work. Letrozole (Femara) works to lower estrogen production and is used for treating BC in postmenopausal women.  

It was unknown if taselisib in combination with letrozole would increase response to treatment for patients with early breast cancer.  

This study involved 334 postmenopausal women with estrogen-receptor (ER) positive, HER2 negative, stage I – III, operable BC. 168 patients received letrozole and placebo (LP group). 166 patients received letrozole and taselisib (LT group). Patients received these treatments for 16 weeks and surgery followed. Patients were followed for an average of 4.9 months.  

An objective response (OR) is a measurable response (tumor shrinkage). 50% of patients in the LT group achieved an OR compared to 39% of patients in the LP group. 56% of patients with a PIK3CA mutant breast cancer in the LT group achieved an OR compared to 38% of patients with a PIK3CA mutant in the LP group.  

A pathological complete response (PCR) is when there are no signs of cancer in tissue samples removed after neoadjuvant treatment. There was no significant difference in PCR between the two groups – in the overall population or the PIK3CA mutant group.  

In the LT group, the most common severe side effects were gastrointestinal (8%), infections (5%), and skin reactions (5%). In the LP group, 2% of patients had severe blood vessel problems, 1% had gastrointestinal disorders and 1% had severe infections and infestations.  

Serious side effects were more common in the LT group than in the LP group. In the LT group, 5% of patients experienced infections and 4% experienced gastrointestinal effects. In the LP group, 1% experienced severe postoperative wound and hematoma (clot) infection, 1% experienced life-threatening brain dysfunction from high blood pressure, 1% experienced severe acute heart failure and 1% experienced severe breast pain.  

This study concluded that neoadjuvant treatment with letrozole and taselisib increased response in patients with hormone receptor-positive, NER2-negative, early breast cancer.  

This study had a short follow-up period. Further studies of longer duration are required. This study was funded by Genentech and F Hoffmann-La Roche, the developers of taselisib.