t have PIK3CA mutations identified inplasma specimen.
Patients received either PIQRAY (300 mg) or placebo orally once daily on a continuous basis, plus fulvestrant(500 mg) administered intramuscularly on Cycle 1, Days 1 and 15, and then on Day 1 of every 28-day cycle.
Patients received treatment until radiographic disease progression or unacceptable toxicity. Tumor assessmentswere performed every 8 weeks for the first 18 months and every 12 weeks thereafter.
The median age of patients was 63 years (range 25 to 92). Most patients were women (99.8%) and most patientswere White (66%), followed by Asian (22%), Other/Unknown (10%), Black or African American (1.4%), andAmerican Indian or Alaskan Native (0.9%). Baseline ECOG performance status was 0 (68%) or 1 (32%).
Patient demographics for those with PIK3CA-mutated tumors were generally representative of the broaderstudy population. The median duration of exposure to PIQRAY plus fulvestrant was 8.2 months with 59% ofpatients exposed for > 6 months.
The majority of patients (98%) received prior hormonal therapy as the last treatment (48% metastatic setting,52% adjuvant setting). Primary endocrine resistance, defined as relapsed within 24 months on adjuvantendocrine therapy or progression within 6 months on endocrine therapy for advanced disease, was observed in
13% of patients and secondary endocrine resistance, defined as relapsed after 24 months on adjuvant endocrinetherapy, relapsed within 12 months of the end of adjuvant endocrine therapy, or progression after 6 months onendocrine therapy for advanced disease, was observed in 72% of patients.The major efficacy outcome was investigator-assessed progression-free survival (PFS) in the cohort with aPIK3CA mutation per Response eva luation Criteria in Solid Tumors (RECIST) v1.1. Additional efficacy
outcome measures were overall response rate (ORR) and overall survival (OS) in the cohort with a PIK3CAmutation.
Efficacy results for the cohort with a PIK3CA mutation in tumor tissue are presented in Table 8 and Figure 1.
PFS results for the cohort with a PIK3CA mutation by investigator assessment were supported by consistentresults from a blinded independent review committee (BIRC) assessment. Consistent results were seen inpatients with tissue or plasma PIK3CA mutations. At the time of final PFS analysis, 27% (92/341) of patientshad died, and overall survival follow-up was immature.
No PFS benefit was observed in patients whose tumors did not have a PIK3CA tissue mutation (HR = 0.85;95% CI: 0.58, 1.25).
Table 8: Efficacy Results in SOLAR-1 (Per Investigator Assessment of Patients with a PIK3CA TumorMutation)
PIQRAY plus fulvestrant Placebo plus fulvestrant
Progression-free survival N = 169 N = 172
Number of PFS events – n (%) 103 (61) 129 (75)
Median PFS months (95% CI) 11.0 (7.5, 14.5) 5.7 (3.7, 7.4)
Hazard ratio (95% CI) 0.65 (0.50, 0.85)
p-value1 0.0013
Overall Response Rate N = 126 N = 136
ORR2
(95% CI) 35.7 (27.4, 44.7) 16.2 (10.4, 23.5)
1 Both log-rank test and Cox proportional hazards model are stratified by prior CDK4/6 inhibitor usage and presence of lung/liver metastases. P-value was compared
to prespecified Haybittle-Peto stopping boundary (two-sided p ≤ 0.0398).
2 ORR = percentage of patients with confirmed Complete Response or Partial Response with measurable disease at baseline.
Figure 1: Progression Free Survival in SOLAR-1 (Per Investigator Assessment of Patients wi |
