Table 2.
Degree of BRCA1 methylation in HGSOC where a pre-treatment biopsy was available for analysis in the ARIEL2 Part 1 clinical trial
Patient # | Archival sample | Pre-treatment biopsy | PFS (months) | Best confirmed response | ||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
BRCA1me status | Estimated BRCA1mea | Neoplastic cellularity | BRCA1 CN | LOH FM/BROCA | BRCA1me status | Estimated BRCA1mea | Neoplastic cellularity | BRCA1 CN | LOH FM/BROCA | |||
1 | HOM | 84% | 60% | 2 | Yes/yes | NO | 0% | 50% | 2 | Yes/– | 20.1 | SD |
2 | HET | 45% | 70.6% | 2 | Yes/– | NO | 0% | 34% | 4 | Yes/– | 1.8 | PD |
7 | HET b | 13% | 40% | 2 | Yes/– | HET | 55% | 30% | 2 | Yes/no | 14.2 | PR |
8 | HET | 41% | 68.9% | 2 | Yes/no | HET | 34% | 63.1% | 2 | Yes/no | 16.1 | SDc |
14 | – | – | – | – | – | HOM d | 77.1% | 20% | NA | –/– | 7.7 | CR |
15 | HOM | 75.3% | 70% | 1 | Yes/– | HOM d | 76.4% | 20% | 1 | Yes/– | 3.6 | SD |
16 | HET b,d | 8.4% | 20% | NA | –/– | HOM | 74.6% | 64.2% | 1 | Yes/– | 18.3 | PR |
17 | HET | 34.9% | 33.5% | NA | –/yes | HOM | 74.0% | 62.4% | 1 | Yes/no | 4.7 | PR |
18 | HOM | 98.5% | 55.8% | 2 | Yes/– | HOM | 85.6% | 64.2% | 3 | Yes/– | 17.2 | PR |
19 | HOM | 92.4% | 60% | 2 | Yes/yes | HOM | 101.2% | 83.6% | 2 | Yes/yes | 14.5 | SD |
20 | HOM | 99.3% | 52.3% | 1 | Yes/yes | HOM | 91.7% | 30% | 2 | Yes/– | 14.6 | PR |
21 | HOM | 86.5% | 92.7% | 1 | Yes/– | HOM | 76.4% | 64% | 1 | Yes/– | 7.2 | PR |
Neoplastic cellularity and BRCA1 copy number were based on the computational genome-wide copy number estimates, as outlined previously52. Italics—low confidence calls, bold—high confidence calls
BRCA1me BRCA1 promoter methylation, CN copy number, LOH loss of heterozygosity, FM Foundation Medicine T5 test, BROCA—BROCA assay, PFS progression-free survival, HET heterozygous, HOM homozygous, NA not available, PR partial response, PD progressive disease, SD stable disease, CR complete response
aIf both LOH estimations (BROCA and FM) were available and concordant, we estimated BRCA1 methylation % using copy number and neoplastic cellularity, otherwise we used neoplastic cellularity
bLow BRCA1 methylation %
cOngoing without response
dLow neoplastic cellularity