Randomized phase II trial of weekly paclitaxel vs. cediranib-olaparib (continuous or intermittent schedule) in platinum-resistant high-grade epithelial ovarian cancer

• Published in: Gynecologic oncology Vol. 164; no. 3; pp. 505 - 513
• Main Authors: Colombo, Nicoletta, Tomao, Federica, Benedetti Panici, Pierluigi, Nicoletto, Maria Ornella, Tognon, Germana, Bologna, Alessandra, Lissoni, Andrea Alberto, DeCensi, Andrea, Lapresa, Mariateresa, Mancari, Rosanna, Palaia, Innocenza, Tasca, Giulia, Tettamanzi, Francesca, Alvisi, Maria Francesca, Rulli, Eliana, Poli, Davide, Carlucci, Luciano, Torri, Valter, Fossati, Roldano, Biagioli, Elena
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-03-2022
• Subjects: Cediranib; Olaparib; Ovarian cancer; Phase II; Randomized; Phase II; Olaparib; Randomized; Cediranib; Ovarian cancer
• ISSN: 0090-8258; 1095-6859
• DOI: 10.1016/j.ygyno.2022.01.015

Previous findings showed that cediranib-olaparib increased PFS in women with recurrent platinum-sensitive ovarian cancer compared to olaparib alone.
BAROCCO trial randomized 123 patients: 80mg/m2 paclitaxel weekly up to 24 weeks (control), olaparib 300mg tablets twice daily together with 20mg cediranib daily (continuous schedule) or with 20mg cediranib 5 days/week (intermittent schedule) until progression. The primary objective was the PFS comparison between each experimental arm and the control (alpha one-sided 5%; power 80%; HR 0.5).
The median platinum-free interval was 1.9 months, 60% of patients had been pretreated with 3 or more chemotherapy lines. Median PFS for paclitaxel, the continuous, and the intermittent schedules were 3.1, 5.6, and 3.8 months. The HR for PFS in the continuous arm vs control was 0.76 (90% CI: 0.50–1.14, p = 0.265). The HR for PFS in the intermittent arm vs control was 1.03 (90% CI: 0.68–1.55, p = 0.904). Treatment was discontinued due to adverse events in 15%, 20%, and 5% of patients in the control, continuous and intermittent arms. Grade ≥ 3 anemia and diarrhea and hypertension of any grade occurred only in the experimental arms, and peripheral neuropathies and alopecia only in the control arm. Five serious adverse drug reactions occurred and two were fatal: one in the control and one in the continuous arm.
The combination of cediranib-olaparib was not superior to chemotherapy in terms of PFS in heavily pretreated platinum-resistant ovarian cancer patients. However, this oral doublet, is active and may offer a non-chemotherapy option in this difficult to treat population.
IRFMN-OVA-7289, EudraCT: 2016–003964-38, NCT03314740.
•The superiority of cediranib-olaparib combination over the standard chemotherapy was not demonstrated.•The intermittent schedule did not show any toxicity benefit and it seemed to have a lower activity than the continuous.•Despite the negative result, cediranib-olaparib combination is an active and feasible non-chemotherapy oral regimen.