Custirsen: Disappointment so far despite a strong biological rationale

There is an unmet need for novel molecular targets and therapies to improve survival in patients with metastatic castrate-resistant prostate cancer (mCRPC).

There is an unmet need for novel molecular targets and therapies to improve survival in patients with metastatic castrate-resistant prostate cancer (mCRPC). Clusterin overexpression in many cancer types results in resistance to a number of chemotherapeutic agents through cytoprotective and anti-apoptotic means. Depletion of clusterin could therefore potentially increase the efficacy of existing treatments. Custirsen is an antisense oligonucleotide targeting secretory clusterin expression that was linked to survival improvements in phase II trials of mCRPC1,2 and untreated lung cancer.3 

The eagerly awaited results of the phase III AFFINITY trial of custirsen plus cabazitaxel/ prednisone in mCRPC were reported yesterday by Professor Karim Fizazi of the Institut  Gustave Roussy, Villejuif, France (Abstract LBA9_PR). Addition of custirsen did not significantly improve overall survival compared with cabazitaxel/prednisone in the total population (n=635; 14.2 months versus  13.4 months, respectively; p=0.529) or  in a poor prognosis subgroup (n=392; 11.1 months versus 10.9 months, respectively; p=0.470). Similar results were reported previously in SYNERGY (custirsen plus docetaxel/prednisone in mCRPC).

The question of whether custirsen plus docetaxel is effective in patients with lung cancer will be answered by the ENSPIRIT trial, due to report in 2017.

  1. Chi KN, et al. J Clin Oncol 2010;28:4247–54
  2. Saad F, et al. Clin Cancer Res 2011;17:5765–73
  3. Laskin JJ, et al. J Thorac Oncol 2012;7:579–86

This article appeared in the Tuesday edition of the Daily Reporter