ICON-9

The randomised phase III ICON-9 study evaluates the addition of the an anti-VEGF agent cediranib to the PARP inhibitor olaparib in the maintenance treatment of patients with high grade platinum-sensitive recurrent ovarian cancer who responded to chemotherapy. During ESMO 2024, Dr Shibani Nicum (University College London, London, UK) presented the results of this trial as a late breaking abstract. In this video, Dr Nicum discusses these data with Prof Dr Christine Gennigens, medical oncologist at the CHU de Liège in Belgium.

ICON-9 included patients with relapsed, platinum-sensitive ovarian, fallopian tube, or primary peritoneal cancer who received no more than 2 prior treatment lines and were in partial or complete response following at least 4 cycles of chemotherapy. Patients were randomly assigned to receive olaparib alone (300mg bid) or in combination with cediranib (20 mg od). Patients in the study were allowed to be pretreated with bevacizumab, but prior PARP-inhibition was not allowed.

The median age of the enrolled patients was 63 years, the vast majority had a serous histology (~97%) and almost 9 out of 10 had received 6 cycles of second-line chemotherapy. Furthermore, about a third of patients previously received bevacizumab, three quarters were BRCA wildtype and about 12% previously underwent surgery.

In general, the combination of olaparib and cediranib was well-tolerated with only 13.4% of patients stopping the treatment for reasons of toxicity (vs. 10.7% with olaparib alone). Unfortunately, the study did not meet its primary endpoint with a HR for progression-free survival (PFS) of 0.84 (95%CI: 0.65-1.07). The median PFS was reported at 13.9 months with the combination as compared to 11.0 months with olaparib alone. Also when looking at the data in function of the BRCA mutation status, the study failed to show a benefit with the cediranib-olaparib combination. Commenting on this finding, Dr Nicum did mention that recruitment for this trial was hampered by the COVID pandemic which resulted in a lower than planned patient number. As a result, it could be that the study lacked the statistical power to show a difference in the BRCA wildtype population. Further analyses of this trial are currently underway to assess whether the HRD status, or TIE2 levels can identify patients who derive benefit from addition of cediranib to the olaparib maintenance treatment.