Results from the SOLAR-1 trial
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 treatment with an aromatase-based inhibitor (with or without a cyclin-dependent kinase 4/6 inhibitor). 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 (1).
SOLAR-1 showed that in patients whose tumors harbored specific PIK3CA mutations (as determined by Clinical Trial Assay), treatment with PIQRAY plus fulvestrant led to a statistically significant improvement in PFS, compared to patients receiving placebo plus fulvestrant (11 months vs. 5.7 months), and conferred an estimated 35% risk reduction in disease progression or death (1).
The importance of establishing PIK3CA mutation status when identifying patients for treatment is therefore clear.
therascreen PIK3CA RGQ PCR Kit clinical performance
Results using FFPE tissue specimens
Analysis of a subset of the study data, on the basis of PIK3CA mutant-positive results obtained from testing with the therascreen PIK3CA RGQ PCR Kit only (347 patients; FFPE tissue samples), 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 (2).
By contrast, PFS was also estimated in the population determined to be PIK3CA mutation-negative by the therascreen PIK3CA RGQ PCR Kit and no PFS benefit was observed in those patients (HR = 0.85; 95% CI: 0.58, 1.25).
The primary PFS analysis for clinical utility of the therascreen PIK3CA RGQ PCR Kit demonstrated similar clinical efficacy to that determined in the SOLAR-1 study.
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).>
Table 1. Correspondence table between therascreen PIK3CA RGQ PCR Kit tissue results and therascreen PIK3CA RGQ PCR Kit plasma results
| ||therascreen PIK3CA RGQ PCR Kit tissue |
|therascreen PIK3CA |
RGQ PCR Kit plasma
|Positive ||Negative ||Invalid ||Total |
|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.>
Table 2. Agreement between therascreen PIK3CA RGQ PCR Kit plasma results and therascreen PIK3CA RGQ PCR Kit tissue results using the therascreen PIK3CA RGQ PCR Kit tissue results as reference
|Measure of agreement ||Percent agreement (N) ||95% CI* |
|Positive percent agreement ||55% (179/328) ||(49.0, 60.1) |
|Negative percent agreement ||97% (209/215) ||(94.0, 99.0) |
|Overall percent agreement ||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.