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Immunotherapy disappoints in prostate cancer
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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
Trial | Prostate cancer setting | Design |
---|---|---|
Keytruda (Merck & Co) | ||
Keynote-921 | 2nd-line (post Xtandi/Zytiga) mCRPC | Docetaxel combo, vs docetaxel |
Keylynk-010 | 3rd-line (post Xtandi/Zytiga + chemo) mCRPC | Lynparza combo, vs Xtandi/Zytiga |
Keynote-991 | 1st-line hormone-sensitive | Xtandi + ADT combo, vs Xtandi + ADT |
Keynote-641 | 1st-line (but allowed some prior Zytiga) mCRPC | Xtandi combo, vs Xtandi |
Opdivo (Bristol Myers Squibb) | ||
Checkmate-7DX | 2nd-line (post Xtandi/Zytiga) mCRPC | Docetaxel combo, vs docetaxel |
Tecentriq (Roche) | ||
Imbassador-250 | 3rd-line (post Zytiga + taxane) mCRPC | Xtandi combo, vs Xtandi |
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