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Checkpoint immunotherapy transformed several cancers and did almost nothing here. In 258 men with advanced prostate cancer, about 1 in 20 had a response, and whether the tumour expressed PD-L1 made no difference.
Emmanuel Antonarakis, Johann de Bono and the KEYNOTE-199 investigators gave pembrolizumab 200 mg every three weeks to 258 men with metastatic castration-resistant prostate cancer who had already had docetaxel and at least one targeted endocrine therapy, in three parallel cohorts: measurable PD-L1-positive disease, measurable PD-L1-negative disease, and bone-predominant disease irrespective of PD-L1.
The response rates, 5 percent and 3 percent in the two measurable cohorts, are the clearest statement available of why prostate cancer is called an immunologically cold tumour, and they sit consistently with the genomics: a median tumour mutational burden of 2.6 mutations per megabase and only 4 percent mismatch repair deficiency (paper-chung-comprehensive-genomic-profiling-prostate-jco-po-2019). The responses that did occur were durable, which is why the field keeps returning to the question with combinations rather than abandoning it.
The measured size of the immunotherapy problem in prostate cancer: a response rate in the low single figures, no signal from PD-L1 expression, and durable benefit in a small subgroup nobody can yet identify prospectively. Any claim that immunotherapy is coming to prostate cancer has to explain this trial.
What a prostate cancer sequencing report looks like in practice, and the numerical basis for two clinical rules: do not expect checkpoint immunotherapy to work unless the tumour is mismatch repair deficient, and do not treat a CDK12 alteration as if it were a BRCA alteration.
One treatment page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.
Shares Johann de Bono, 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, Docetaxel, Metastatic castration-resistant prostate cancer and the tag prostate-evidence.
Shares Johann de Bono, Prospective comprehensive genomic profiling of 3,476 primary and metastatic prostate tumours, 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 and the tag prostate-evidence.
Shares Johann de Bono, 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 Prospective comprehensive genomic profiling of 3,476 primary and metastatic prostate tumours, 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, Docetaxel and the tag prostate-evidence.
Shares Johann de Bono, 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.
Shares Tumour mutational burden (TMB), 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, No one can predict who responds to immunotherapy, Metastatic castration-resistant prostate cancer and the tag prostate-evidence.
Shares Johann de Bono, 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.