The SOLAR-1 study (CBYL719C2301) was a randomized, double-blinded, placebo-controlled, international, multicenter Phase III clinical trial that compared treatment with PIQRAY plus fulvestrant with placebo plus fulvestrant in men and postmenopausal women with hormone receptor-positive, HER2-negative advanced breast cancer that had progressed on or after aromatase inhibitor treatment. A total of 572 breast cancer patients were enrolled into two cohorts, with or without a PIK3CA mutation. Patients were randomized to receive PIQRAY 300 mg plus fulvestrant or placebo plus fulvestrant in a 1:1 ratio. The primary endpoint was progression-free survival (PFS) determined using RECIST v1.1 criteria, based on investigator assessment.
Results using FFPE tissue specimens
SOLAR-1 showed that in patients whose tumors harbored specific PIK3CA mutations, treatment with PIQRAY plus fulvestrant prolonged median PFS by a clinically meaningful 5.3 months (11 months overall) compared with treatment with placebo plus fulvestrant, and conferred an estimated 35% risk reduction in disease progression or death. Analysis of the CDx PIK3CA mutant-positive patient subset (347 patients) demonstrated that those receiving PIQRAY plus fulvestrant had an estimated 36% lower risk of disease progression or death (HR = 0.64; 95% CI: 0.48, 0.85) than patients receiving placebo plus fulvestrant.
By contrast, PFS was also estimated in the therascreen PIK3CA RGQ PCR Kit-negative population and no PFS benefit was observed in those patients (HR = 0.85; 95% CI: 0.58, 1.25).
The importance of establishing PIK3CA mutation status when identifying patients for treatment with PIQRAY plus fulvestrant is therefore clear; only patients whose tumors harbor actionable PIK3CA mutations are likely to experience a clinically meaningful increase in PFS.
Results using plasma specimens
K2EDTA anticoagulated peripheral venous whole blood clinical plasma specimens collected from breast cancer patients randomized in SOLAR-1 prior to initiation of study treatment (baseline) were tested retrospectively with the therascreen PIK3CA RGQ PCR Kit to evaluate concordance between tissue and plasma results.
Of the 328 therascreen PIK3CA RGQ PCR Kit tissue-positive patients, 179 were therascreen PIK3CA RGQ PCR Kit plasma-positive. Of the 215 therascreen PIK3CA RGQ PCR Kit tissue-negative patients, 209 were therascreen PIK3CA RGQ PCR Kit plasma-negative. There were no invalid plasma results (Table 1).
|Positive || 179 || 6 || 1 || 186 |
|Negative || 149 || 209 || 5 || 363 |
|Invalid || 0 || 0 || 0 || 0 |
|Total || 328 || 215 || 6 || 549 |
Agreement (PPA, NPA and OPA) between the therascreen PIK3CA RGQ PCR Kit plasma and therascreen PIK3CA RGQ PCR Kit tissue results was calculated using the therascreen PIK3CA RGQ PCR Kit tissue results as reference (Table 2). The point estimates of PPA, NPA and OPA were 55%, 97% and 72%, respectively.
|Positive percent agreement (PPA) || 55% (179/328) || 49.0%, 60.1% |
|Negative percent agreement (NPA)* || 97% (209/215) || 94.0%, 99.0% |
|Overall percent agreement (OPA) || 72% (388/543) || 67.5%, 75.2% |
The therascreen PIK3CA RGQ PCR Kit therefore enables reliable selection of breast cancer patients with PIK3CA alterations who may be eligible for treatment with PIQRAY.