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The trial that got rucaparib approved for prostate cancer. In 115 men with a BRCA fault whose cancer had already been through hormone drugs and chemotherapy, around half had their tumours shrink or their PSA halve.
Wassim Abida and the TRITON2 investigators treated men with metastatic castration-resistant prostate cancer and a deleterious BRCA1 or BRCA2 alteration with rucaparib 600 mg twice daily, after progression on one or two androgen receptor-directed therapies and one taxane. The efficacy and safety populations comprised 115 men.
The result supported accelerated approval in the United States in May 2020, on a single-arm response rate, three years before TRITON3 provided the randomised confirmation. Response rates were similar whether the BRCA alteration was germline or somatic and whether it was BRCA1 or BRCA2, although prostate-specific antigen responses were higher with BRCA2. That germline and somatic alterations behave the same is the practical reason tumour sequencing, not just a blood test for inherited faults, belongs in this disease.
The trial behind the second PARP inhibitor licensed in prostate cancer, and the evidence that a somatic BRCA alteration predicts response as well as an inherited one. Together with TOPARP-A it is why tumour as well as germline sequencing is recommended in metastatic disease.
The randomised proof for PARP inhibition in BRCA-altered prostate cancer, and the clearest evidence that the homologous recombination repair gene list should not be used as a single yes-or-no test. ATM-altered disease needs a different answer, and does not yet have one.
The first molecularly stratified treatment in prostate cancer, and the proof that the synthetic lethality that works in ovarian and breast cancer works here too. Every PARP inhibitor now licensed in prostate cancer traces back to this trial.
Shares TOPARP-A: DNA-repair defects and olaparib in metastatic prostate cancer, TRITON3: rucaparib or physician's choice in metastatic castration-resistant prostate cancer, Test every man for DNA repair faults on the day his prostate cancer is found to have spread, not three treatments later, Homologous recombination deficiency (HRD) and the tag prostate-evidence.
Shares TRITON3: rucaparib or physician's choice in metastatic castration-resistant prostate cancer, Genome-wide loss of heterozygosity (gLOH), Test every man for DNA repair faults on the day his prostate cancer is found to have spread, not three treatments later, Homologous recombination deficiency (HRD) and the tag prostate-evidence.
Shares TOPARP-A: DNA-repair defects and olaparib in metastatic prostate cancer, Test every man for DNA repair faults on the day his prostate cancer is found to have spread, not three treatments later, Homologous recombination deficiency (HRD), Prostate cancer roadmap: from Huggins and the discovery that a cancer can depend on a hormone, through the PSA epidemic and what it cost, the androgen receptor drugs, the DNA repair subset and PSMA, to a 2032 registry watch and the tag prostate-evidence.
Shares PSA (prostate-specific antigen), Prostate cancer roadmap: from Huggins and the discovery that a cancer can depend on a hormone, through the PSA epidemic and what it cost, the androgen receptor drugs, the DNA repair subset and PSMA, to a 2032 registry watch, Metastatic castration-resistant prostate cancer, Journal of Clinical Oncology and the tag prostate-evidence.
Shares PSA (prostate-specific antigen), Prostate cancer roadmap: from Huggins and the discovery that a cancer can depend on a hormone, through the PSA epidemic and what it cost, the androgen receptor drugs, the DNA repair subset and PSMA, to a 2032 registry watch, Metastatic castration-resistant prostate cancer, Prostate cancer and the tag prostate-evidence.
Shares PSA (prostate-specific antigen), Prostate cancer roadmap: from Huggins and the discovery that a cancer can depend on a hormone, through the PSA epidemic and what it cost, the androgen receptor drugs, the DNA repair subset and PSMA, to a 2032 registry watch, Biomarkers are not validated or standardised, Prostate cancer and the tag prostate-evidence.
Shares PSA (prostate-specific antigen), Prostate cancer roadmap: from Huggins and the discovery that a cancer can depend on a hormone, through the PSA epidemic and what it cost, the androgen receptor drugs, the DNA repair subset and PSMA, to a 2032 registry watch, Biomarkers are not validated or standardised, Metastatic castration-resistant prostate cancer and the tag prostate-evidence.
Shares Prostate cancer roadmap: from Huggins and the discovery that a cancer can depend on a hormone, through the PSA epidemic and what it cost, the androgen receptor drugs, the DNA repair subset and PSMA, to a 2032 registry watch, Biomarkers are not validated or standardised, Metastatic castration-resistant prostate cancer, Journal of Clinical Oncology and the tag prostate-evidence.