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
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 |
373