PS1-3Alpelisib (ALP)+fulvestrant (FUL) in patients from Japan with advanced breast cancer: Subgroup analysis of SOLAR-1 trial

Abstract Background Hyperactivation of PI3K pathway can occur due to PIK3CA mutations, which is present in ∼40% of patients (pts) with HR+, HER2- ABC. In SOLAR-1 (NCT02437318) trial, ALP+FUL significantly extended progression-free survival (PFS) vs placebo (PBO)+FUL in the PIK3CA-mutant (mut) cohort (median 11.0 vs 5.7 months; HR = 0.65; P  Methods Men and postmenopausal women with HR+, HER2- ABC and recurrence/progression on/after prior aromatase inhibitor were randomized (1:1) to ALP (300 mg/day)+FUL (500 mg every 28 days+Cycle 1 Day 15) or PBO+FUL. This trial consisted of the PIK3CA-mut cohort for confirmatory purpose and the PIK3CA non-mutant (non-mut) cohort for proof of concept purpose. Primary endpoint was locally assessed PFS in the PIK3CA-mut cohort. Safety was assessed in the total population. Results Among 572 pts, 68 pts were enrolled in Japan; 36 pts in the PIK3CA-mut cohort received ALP+FUL (n = 17) or PBO+FUL (n = 19), and 32 pts in the non-mut cohort received ALP+FUL (n = 15) or PBO+FUL (n = 17). In JPN pts, ALP+FUL did not improve PFS in the mut cohort (median 9.6 vs 9.2 months; HR = 0.78). Duration of ALP exposure was shorter (median 1.7 months in JPN vs 5.5 months in overall population). Most frequent all-grade adverse events (JPN vs overall population) were rash (75.0% vs 53.9%), hyperglycemia (68.8% vs 65.8%), gastrointestinal toxicities (65.6% vs 75.4%), hypersensitivity and anaphylactic reaction (25.0% vs 16.5%). Severe cutaneous reactions (i.e. Stevens-Johnson syndrome, erythema multiforme) were observed only in JPN pts (n = 4; 12.5%). Conclusions Among pts from Japan, ALP+FUL showed no clinically meaningful improvement in PFS for pts with PIK3CA mut status and ALP exposure was much shorter than of the overall population. The incidence of cutaneous reactions was higher in Japanese vs overall population.