Curtirsen and cabazitaxel combination failure
Combining curtirsen with cabazitaxel fails to improve overall survival in patients with metastatic castration-resistant prostate cancer that has progressed after docetaxel.
Custirsen is a second generation, highly specific antisense oligonucleotide that inhibits the production of clusterin, an anti-apoptotic protein that is upregulated in response to chemotherapy and that confers treatment resistance.
In the phase 3 AFFINITY trial reported in The Lancet Oncology median overall survival was 14·1 months in the cabazitaxel and prednisone plus custirsen group versus 13·4 months in the cabazitaxel and prednisone group (HR 0·95; 95% CI 0·80–1·12).
In an accompanying editorial, Rahul Aggarwal from the University of California says, ‘AFFINITY joins an extensive list of negative phase 3 trials of taxane-based combinations in unselected patients with metastatic castration-resistant prostate cancer.’ Moving forward we need to make greater use of biomarkers to identify subsets of patients who are most likely to benefit from treatment in these studies, he concludes.