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In 115 men whose prostate cancer carried a BRCA fault, a PARP inhibitor shrank measurable tumour in about half and halved PSA in more than half.
TRITON2 enrolled men who had progressed after one to two lines of next-generation androgen receptor-directed therapy and one taxane-based chemotherapy for metastatic castration-resistant prostate cancer, and treated them with rucaparib 600 mg twice daily. The efficacy and safety populations included 115 men with a deleterious BRCA alteration with or without measurable disease. Confirmed objective response rates were 43.5% by independent radiology review, 27 of 62 men with measurable disease, and 50.8% by investigator assessment, 33 of 65. The confirmed PSA response rate, a fall of at least half, was 54.8%, 63 of 115. Response rates were similar for germline and somatic alterations and for BRCA1 and BRCA2 alterations, while a higher PSA response rate was observed with BRCA2. The most frequent grade 3 or higher treatment-emergent adverse event was anaemia, in 29 of 115 men, 25.2%.
It is the evidence behind the narrowest of the four prostate PARP inhibitor eligibility lists, and its germline-against-somatic result matters practically: a somatic BRCA alteration found on a tumour panel qualifies a man for the drug just as an inherited one does.
Shares Base excision repair, PARP & alkylation damage, Tumour (somatic or germline) BRCA1/2 mutation and HRR gene alterations, Homologous recombination repair gene mutation in prostate cancer, Synthetic lethality: paired dependencies.
Shares Base excision repair, PARP & alkylation damage, Synthetic lethality: paired dependencies, Germline BRCA mutation (gBRCA), Double-strand break repair: HR versus end joining.
Shares Rucaparib, Tumour (somatic or germline) BRCA1/2 mutation and HRR gene alterations, Homologous recombination repair gene mutation in prostate cancer, Germline BRCA mutation (gBRCA).
Shares Homologous recombination repair gene mutation in prostate cancer, Germline BRCA mutation (gBRCA), Double-strand break repair: HR versus end joining, Homologous recombination deficiency (HRD).
Shares Germline BRCA mutation (gBRCA), Double-strand break repair: HR versus end joining, Homologous recombination deficiency (HRD), Germline vs somatic mutations.
Shares Germline BRCA mutation (gBRCA), Double-strand break repair: HR versus end joining, Homologous recombination deficiency (HRD), Germline vs somatic mutations.
Shares Germline BRCA mutation (gBRCA), Double-strand break repair: HR versus end joining, Homologous recombination deficiency (HRD), Germline vs somatic mutations.
Shares Tumour (somatic or germline) BRCA1/2 mutation and HRR gene alterations, Homologous recombination repair gene mutation in prostate cancer, Double-strand break repair: HR versus end joining, Homologous recombination deficiency (HRD).