Patients with previously treated metastatic, castration-resistant prostate cancer (mCRPC) see no benefit when custirsen is added to the combination of Jevtana (cabazitaxel) and prednisole, according to the results of a Phase 3 clinical trial.
The data, presented at the recent European Society for Medical Oncology (ESMO) 2016 Congress, show that patients treated with the custirsen, Jevtana, and prednisone combination have similar survival rates compared to those treated with Jevtana and prednisone alone.
“Despite the negative outcome of the trial, the evaluation of custirsen in prostate cancer was conducted on the basis of solid preclinical and clinical evidence supporting anti-tumor activity,” principal investigator Karim Fizazi, head of the Department of Cancer Medicine at the Institut Gustave Roussy, in Villejuif, France, said in a press release.
Previous data from a Phase 2 trial (NCT00258388) suggested that custirsen could improve the outcomes of mCRPC patients when combined with chemotherapy, and a Phase 3 trial of custirsen in combination with Taxotere (docetaxel) showed promising results in patients with more aggressive cancers.
“Given the results observed using a taxane as either first-line or second-line chemotherapy in castration resistant prostate cancer, the hypothesis was that combination with custirsen may decrease taxane resistance and enhance the survival benefit of taxane therapy,” said Dr. Cora Sternberg, chief of the Department of Medical Oncology at San Camillo Forlanini Hospital, in Rome, Italy.
To assess whether custirsen could be combined with Jevtana and prednisone in mCRPC patients who had received prior Taxotere treatment, OncoGenex Technologies and researchers from the United States, France, and Canada conducted the AFFINITY trial (NCT01578655).
The open-label Phase 3 trial enrolled 635 patients who were randomized to receive 21-day cycles of either custirsen plus Jevtana/prednisone or placebo plus Jevtana/prednisone for ten cycles, or until disease progression or unacceptable toxicity occurred.
Results revealed that the custirsen and placebo side of the study had similar overall survival rates, with custirsen showing a median overall survival of 14.2 months versus 13.4 months from the placebo side.
Among 62 percent of patients who met the criteria for poor prognosis, similar results were observed — the custirsen arm showed a median overall survival of 11.1 months versus 10.9 months in the placebo group.
Also, similar numbers of patients discontinued therapy in the custirsen and placebo arms because of disease progression (28.9% versus 25%) or adverse effects (21.9% versus 18.9%). Most frequently observed adverse effects included anemia, neutropenia, fatigue, bone pain, and weakness.
“There was a strong rationale for adding custirsen to chemotherapy to overcome resistance but unfortunately the final results were negative. We likely need even more robust biological molecular stratification before launching Phase 3 trials,” said Sternberg.
Fizazi noted that despite the negative outcome of the trial, custirsen may still be a promising therapy for patients with lung cancer.
“Custirsen remains a viable candidate currently being evaluated for the treatment of non-small cell lung cancer, as failure in one tumor type does not predict the outcome of trials in other indications,” he said.