A near doubling of progression-free survival (PFS) is one of the preliminary findings from a phase 2 study of the first oral combination of drugs for recurrent platinum-sensitive ovarian cancer, say researchers who reported at the annual meeting of the American Society of Clinical Oncology in June 2014.
The study, sponsored by the National Cancer Institute (NCI), compared a combination of olaparib and cediranib, with olaparib alone. Olaparib inhibits the poly (ADP-ribose) polymerase (PARP) enzyme, which is involved in many cell functions, including repair of DNA damage. Cediranib is an anti-angiogenic drug. Both drugs are active in recurrent ovarian cancer. Olaparib has been used as monotherapy and was recently granted Priority Review by the FDA for treatment of platinum-sensitive relapsed ovarian cancer in patients with a BRCA gene mutation. In the phase 3 ICON 6 trial, cediranib significantly improved PFS and overall survival in platinum-sensitive relapsed ovarian cancer, compared with chemotherapy alone.
Preclinical studies suggested that the 2 drugs would be synergistic, and an early phase 1 trial showed that the combination was well tolerated, with minimal adverse effects (AEs). Based on those early findings, 90 patients from 9 centers were randomly assigned to 1 of 2 study arms for the phase 2 trial. The first group took olaparib capsules 400 mg twice daily, and the other group took the combination olaparib 200 mg twice daily and cediranib tablets 30 mg once daily. The study arms were stratified by BRCA gene mutation status and whether the patient had received prior anti-angiogenic therapy.
Patients were enrolled from October 2011 to June 2013. As of March 2014, median PFS was 17.7 months for the combination therapy, vs 9.2 months for olaparib alone. The rate of toxicity was higher in the combination group, with fatigue, diarrhea, and hypertension the most common AEs. All AEs were found to be manageable.
Two phase 3 trials are planned for platinum-sensitive and platinum-resistant ovarian cancer based on the results of the phase 1 and 2 trials. The trials will be overseen by one of the new National Cancer Trial Network Groups of the NCI, the NRG Oncology Group.
Source
National Institutes of Health. Clinical trial analysis suggests drug combination may be highly effective in recurrent ovarian cancer. National Cancer Institute Website. http://www.nih.gov/news/health/jun2014/nci-02.htm. Accessed July 17, 2014.
doi: j.ajog.2013.11.039.