(Prostate Cancer) Custirsen Plus Cabazitaxel: ESMO 2016 AFFINITY Phase 3 Trial Results

• October 26, 2016
• 1 min read

At ASCO 2010, J.S. De Bono of Royal Marsden NHS Foundation Trust published results demonstrating that cabazitaxel was effective in prostate cancer patients previously treated with docetaxel. This month at ESMO 2016, Karim Fizazi of Institut Gustave Roussy (France) presented Phase 3 clinical trial results for custirsen.

Custirsen (OGX-011) is a second-generation antisense oligonucleotide that blocks the anti-apoptotic mechanisms in cancer cells. Phase 2 clinical trial results comparing docetaxel alone versus docetaxel plus custirsen showed no significant difference in OS; however, subgroup analysis revealed better recovery outcomes with the combination. Based on this finding, a Phase 3 trial was initiated.

AFFINITY Phase 3 Trial Design:

A total of 635 subjects were enrolled. Eligibility required prior docetaxel treatment for castration-resistant prostate cancer. Patients were randomized to custirsen + cabazitaxel/prednisone versus cabazitaxel/prednisone alone.

• Custirsen arm: Cabazitaxel 25 mg/m² every 21 days + prednisone 10 mg daily + custirsen 640 mg (3 loading doses followed by weekly maintenance)
• Up to 10 treatment cycles in the absence of severe adverse events

Primary endpoints: overall OS and OS in poor-prognosis patients.

Poor-prognosis definition (2 of 5 criteria): Karnofsky PS ≤80%, liver metastases, Hb <12 g/dL, LDH ≥360 IU/L, PSA ≥150 ng/mL. Poor-prognosis patients: custirsen arm 61.5%, control arm 61.9%.

Results:

• Median OS (all patients): Custirsen arm 14.2 months vs. control arm 13.4 months
• No significant difference between arms

Safety:

No particular safety concerns. Grade 3+ adverse events: custirsen arm 76% vs. control arm 66%. Common adverse events included anemia, leukopenia, diarrhea, and back pain.

Conclusion: In previously docetaxel-treated, castration-resistant prostate cancer patients, the addition of custirsen to cabazitaxel did not provide additional therapeutic benefit.

Prostate Cancer | Custirsen | Cabazitaxel | ESMO 2016

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