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Immunotherapy disappoints in prostate cancer

Prostate cancer is an indication so far untapped by checkpoint blockers, and for Bristol Myers Squibb it looks set to remain this way. In its second-quarter release today the company revealed the discontinuation of the phase 3 Checkmate-DX trial, which was testing Opdivo plus docetaxel/prednisone versus docetaxel/prednisone alone in metastatic castration-resistant prostate cancer patients who had progressed on a novel hormone therapy, effectively meaning Xtandi or Zytiga. The trial had a similar design to Merck & Co’s Keynote-921 study of Keytruda – and that failed a year ago. Bristol said Checkmate-7DX did not meet the primary endpoints of radiographic PFS at final analysis, or OS at an interim analysis, and its data-monitoring committee recommended that it be discontinued. For immunotherapy the one glimmer of hope in prostate cancer has come courtesy of Keynote-199, where the best responses apparently came in patients with DNA repair defects, according to the Journal of Clinical Oncology. However, even here efficacy was limited overall.

Notable failures of anti-PD-(L)1 drugs in prostate cancer

TrialProstate cancer settingDesign
Keytruda (Merck & Co)
Keynote-9212nd-line (post Xtandi/Zytiga) mCRPCDocetaxel combo, vs docetaxel
Keylynk-0103rd-line (post Xtandi/Zytiga + chemo) mCRPCLynparza combo, vs Xtandi/Zytiga
Keynote-9911st-line hormone-sensitiveXtandi + ADT combo, vs Xtandi + ADT
Keynote-6411st-line (but allowed some prior Zytiga) mCRPCXtandi combo, vs Xtandi
Opdivo (Bristol Myers Squibb)
Checkmate-7DX2nd-line (post Xtandi/Zytiga) mCRPCDocetaxel combo, vs docetaxel
Tecentriq (Roche)
Imbassador-2503rd-line (post Zytiga + taxane) mCRPCXtandi combo, vs Xtandi

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