DUO-O Trial Shows Efficacy of Triplet Maintenance for Ovarian Cancer

Christina Fotopoulou, MD, PhD, chair in gynaecological cancer surgery in the department of surgery and cancer, faculty of medicine, Imperial College London, discusses the results of the DUO-O trial (NCT03737643) in patients with newly diagnosed ovarian cancer.

The large multicenter phase 3 DUO-O trial randomly assigned patients into 3 arms to receive platinum-based chemotherapy plus bevacizumab (Avastin) and durvalumab (Imfinzi) followed by maintenance bevacizumab, durvalumab, and olaparib (Lynparza); chemotherapy in combination with bevacizumab and durvalumab followed by maintenance bevacizumab and durvalumab; or chemotherapy plus bevacizumab followed by maintenance bevacizumab. The primary end point was progression-free survival (PFS) in the intent-to-treat (ITT) population and in the homologous recombination deficiency (HRD)–positive group.

The study showed a significant improvement in PFS in the ITT and HRD-positive groups with a HR of 0.49 favoring the triplet combination in HRD-positive patients and 0.63 favoring it in the ITT population. It additionally showed a HR of 0.68 in the HRD-negative group favoring the triplet combination arm. Fotopoulou says that no other studies showed a benefit for this group besides the PRIMA study (NCT02655016) of maintenance niraparib (Zejula). That study also had an HR of 0.68, although niraparib was compared with placebo and not an active comparator for maintenance. Fotopoulou says this study shows a role for a maintenance regimen that includes immunotherapy, but the relative toxicity of the DUO-O triplet regimen would also influence the choice to use it.

TRANSCRIPTION:

0:08 | It's a very large multicenter prospective randomized phase 3 study with durvalumab, a PD-L1 inhibitor, bevacizumab, a VEGF inhibitor, and PARP inhibitors, versus bevacizumab alone. These were the 2 main arms that were the primary analysis there was also a second arm with bevacizumab and durvalumab. The primary end point was to see whether there was a survival benefit in the ITT and HRD-positive population.

0:45 | This study is the first study in ovarian cancer, the first IO second-line cancer [study], to show a significant prolongation of the PFS with the HR of 0.68 for the HRD-negative population, which has been always a very challenging target group. So far, it is a group where only the PRIMA and the DUO-O study have shown a benefit. Very interestingly, we see that the hazard ratio in both studies is exactly the same with 0.68. It was very interesting to see it; even though the HR is the same, the difference is the triplet. One has a triplet therapy and the other only 1 [drug], meaning of course that there are also different associations with morbidity and toxicity and heterogenic complications, etc.