Goal To assess overall survival (OS), time to chemotherapy (TTC) and chemotherapy-free
survival (CFS) in patients with and without PIK3CA mutations in MONARCH 2.
Material and method MONARCH 2 was a global, randomized, double-blind phase III trial of abemaciclib+fulvestrant
or placebo+fulvestrant in pre-/perimenopausal (with ovarian suppression) and postmenopausal
women with endocrine therapy resistant HR+, HER2- advanced breast cancer. Results
of PIK3CA mutation status (E542K; E545K; H1047L; H1047R) from baseline ctDNA were available
for 238 patients. Exploratory analyses of OS, TTC and CFS were assessed in patients
with/without PIK3CA mutations using Cox Regression Models with treatment, PIK3CA mutation status and treatment by PIK3CA interaction term as covariates.
Results Abemaciclib+fulvestrant demonstrated a similar OS benefit in PIK3CA mutant (hazard ratio [HR]: 0.57; 95 % confidence interval [CI]: 0.34, 0.96) and PIK3CA wild-type (HR: 0.56; 95 %CI: 0.34, 0.91) versus placebo+fulvestrant. TTC was longer
for abemaciclib+fulvestrant versus placebo+fulvestrant both in PIK3CA mutant (HR:
0.65; 95 %CI: 0.37, 1.18) and PIK3CA wild-type (HR: 0.50; 95 %CI: 0.31, 0.78). CFS
was also longer for abemaciclib+fulvestrant versus placebo+fulvestrant both in PIK3CA
mutant (HR: 0.63; 95 %CI: 0.39, 1.03) and PIK3CA wild-type (HR: 0.53; 95 %CI: 0.35,
0.80).
Summary In this exploratory analysis of MONARCH 2, abemaciclib+fulvestrant demonstrated benefit
in OS, TTC and CFS in patients with and without PIK3CA mutations.
