Baselga J, et al. - Given taselisib (a potent, selective PI3K inhibitor) has enhanced activity in PIK3CA-MUT BC cell lines and confirmed partial responses in PIK3CA-MUT BC as a single-agent or with FULV, researchers evaluated efficacy and safety of taselisib + FULV in patients with ER-positive, HER2-negative, PIK3CA-MUT locally advanced or MBC. Significantly improved investigator-assessed progression-free survival (INV-PFS) was seen with taselisib + FULV vs PBO + FULV in this patient population. Furthermore, the safety profile demonstrated by this treatment regimen was largely consistent with previous studies.

Methods

• In SANDPIPER, a double-blind, placebo (PBO)-controlled, randomized, phase 3 study, researchers randomized 2:1 postmenopausal patients with disease recurrence or progression during or after an aromatase inhibitor to receive taselisib (4 mg oral, QD) or PBO + FULV (500 mg).
• Visceral disease, endocrine sensitivity, and geographic region were included as stratification factors.
• Separate randomization of patients with PIK3CA-MUT tumors, assessed by central cobas PIK3CA Mutation Test, from non-MUT tumors was carried out.
• Investigator-assessed progression-free survival (INV-PFS) in patients with PIK3CA-MUT tumors was the primary endpoint.
• They also assessed objective response rate (ORR), overall survival (OS), clinical benefit rate (CBR), duration of objective response (DoR), PFS by blinded independent central review (BICR-PFS), and safety (all included as secondary endpoints).

Results

• In the PIK3CA-MUT intention-to-treat (ITT) population, randomization of 516 patients was carried out.
• BICR-PFS (HR 0.66) corroborated that taselisib + FULV significantly improved INV-PFS (hazard ratio [HR] 0.70).
• They found that OS was immature.
• Diarrhea (12%), hyperglycemia (10%), colitis (3%), and stomatitis (2%) were documented as the most common grade ≥ 3 adverse events (AEs; preferred terms) in the taselisib + FULV arm in safety-evaluable patients who received ≥ 1 dose of treatment.
• Findings revealed AEs led to more taselisib discontinuations (17% vs 2%) and dose reductions (37% vs 2%) vs PBO.