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Metastatic castration-resistant prostate cancer (mCRPC) is a molecularly heterogeneous disorder with a poor
prognosis.
About 20-30% of patients carry harmful variants in DNA damage repair genes, including those that directly or indirectly play a role in the homologous recombinant repair (HRR) pathway
.
The Phase 3 PROfound study evaluated the efficacy
of olaparib compared to abiraterone or enzalutamide (control) in patients with metastatic castration-resistant prostate cancer carrying HRR gene variants.
The results of an exploratory analysis using ctDNA testing as an additional method to identify patients with mCRPC with HRR gene variants are candidates for olaparib therapy
.
The researchers retrospectively analyzed BRCA1, BRCA2, and ATM variants
in the plasma ctDNA of patients in the PROfound trial.
Only patients in Cohort A (those with positive BRCA/ATM variant validated by tissue testing)
were assessed.
The investigators compared the clinical prognosis of patients in the ctDNA subgroup and cohort A, including radiographic progression-free survival (rPFS).
A cohort ctDNA subgroup rPFS in two treatment groups
Of the 181 (73.
9%) patients in Cohort A, 139 (76.
8%) had test results, of which 111 (79.
9%) were detected as carrying the BRCA/ATM variant
.
Of the patients carrying the BRCA/ATM variant, 73 received olaparib and 38 received control
.
The baseline demographics and characteristics and HRR variation rates of patients carrying BRCA/ATM variants were comparable
to those in Cohort A's intention-to-treat population.
rPFS and OS in the A cohort ctDNA subgroup and the A cohort in the intention-to-treat population
Compared with the control group, the rPFS was longer in the olaparib group (median rPFS: 7.
4 vs 3.
5 months; Risk ratio [HR] 0.
33, p<0.
0001), consistent with Cohort A's intention-to-treat population (HR 0.
34).
In summary, ctDNA testing may be a suitable option
for identifying patients with mCRPC with BRCA/ATM variants who may benefit from olaparib when tumor tissue testing is not feasible or fails.
Original source:
Nobuaki Matsubara, Johann de Bono, David Olmos, et al.
Olaparib Efficacy in Patients with Metastatic Castration-resistant Prostate Cancer and BRCA1, BRCA2 or ATM Alterations Identified by Testing Circulating Tumor DNA.
Clin Cancer Res 2022; https://doi.
org/10.
1158/1078-0432.
CCR-21-3577
