ASCO GU 2025: impact of homologous recombination repair (HRR) gene mutations in metastatic hormone-sensitive prostate cancer (mHSPC)

[Maxone73]

A study on homologous recombination repair (HRR) gene mutations in metastatic hormone-sensitive prostate cancer (mHSPC) found different impacts based on the specific gene altered.

ATM mutations showed no significant effect on time to castration resistance (TTCR) or overall survival (OS), meaning outcomes are similar to non-mutated patients.

BRCA1/2 mutations led to faster progression to castration resistance (shorter TTCR), but OS remained unchanged.

CDK12 mutations, however, were linked to significantly worse outcomes, with faster disease progression and shorter survival. These findings highlight the need for genetic testing to guide treatment, as CDK12-mutated cases may require earlier aggressive intervention or clinical trial enrollment.

prostatewarriors.com/2025/0...

[StayingOptimistic]

any mention of PTEN mutation please?

[Maxone73 in reply to StayingOptimistic]

None that I have seen 🙁

[StayingOptimistic in reply to Maxone73]

Thank you. Keep up the great work. We all appreciate it.

[Maxone73 in reply to StayingOptimistic]

Thanks! I try my best!

[KocoPr]

i see these are somatic mutations.

This is very interesting.

So are they actually saying that if you have a BRCA or ATM mutations it doesn’t matter if they take PARP inhibitors or checkpoint inhibitors?

[Maxone73 in reply to KocoPr]

No, it's just a study based on real data. "Inclusion criteria: de novo mHSPC, tissue biopsy within 90 days of diagnosis, and initiation of androgen deprivation therapy intensification (ADTi) with androgen receptor pathway inhibitor (ARPI) or taxane within 120 days of diagnosis. "

Basically they considered people under doublet therapy till castration resistance, then they measured OS but without specifying which therapy was used in CR setting.