Articles

Genomic profiling of patients with metastatic castration-resistant prostate cancer (mCRPC) for the evaluation of rucaparib: next-generation sequencing (NGS) of tumour tissue and cell-free DNA (cfDNA)

BJMO - 2019, issue 2, february 2019

Brieuc Sautois

Background

The phase 2 TRITON2 (NCT02952534) and phase 3 TRITON3 (NCT02975934) studies are evaluating the poly(ADP-ribose) polymerase inhibitor rucaparib in patients with mCRPC who have a deleterious germline or somatic mutation in BRCA1, BRCA2, ATM, or other DNA damage repair (DDR) gene. Here we present interim results of central genomic screening of tissue samples and plasma cfDNA in TRITON2 and TRITON3.

Methods

Formalin-fixed paraffin-embedded (FFPE) tumour tissue samples were profiled for genomic alterations in 395 genes, and plasma samples were profiled for genomic alterations in 70 genes, using Foundation Medicine, Inc., NGS assays.

Results

As of 2 July 2018, 1311 tumour tissue blocks (73%) and slides (27%) from primary prostate cancer tumours (84%) and metastases (16%) of 1214 patients with mCRPC were processed. The median sample age was 2.8 years (range, 4 days to 21 years). The NGS tissue test failure rate was 32%, mainly (18%) due to insufficient tumour content or DNA. In total, samples from 872 patients were sequenced successfully. Deleterious genomic alterations in BRCA1, BRCA2, and/or ATM were observed in 15% of patients with successfully sequenced samples: BRCA1 (2%), BRCA2 (7%), and ATM (6%).

In parallel, a total of 638 plasma samples from 606 patients with mCRPC progressing on prior therapy were sequenced. The median sample age was 2 days (range, 1-10 days). NGS was successful for 97% of the plasma samples, and in 93% of those, a genomic alteration was detected in at least 1 assayed gene. Deleterious genomic alterations in BRCA1, BRCA2, and/or ATM were observed in 19% of patients with successfully sequenced samples: BRCA1 (2%), BRCA2 (9%), and ATM (12%).

Conclusions

Genomic profiling of both FFPE tumour tissue samples and cfDNA using NGS successfully identified patients with a genomic alteration in a DDR gene for the evaluation of rucaparib in mCRPC. Additional genomic analyses will be presented.

Read more
X