Nicoletta Colombo1, Federica Tomao2, Pierluigi Benedetti Panici3, Maria Ornella Nicoletto4, Germana Tognon5, Alessandra Bologna6, Andrea Alberto Lissoni7, Andrea DeCensi8, Mariateresa Lapresa2, Rosanna Mancari9, Innocenza Palaia3, Giulia Tasca4, Francesca Tettamanzi10, Maria Francesca Alvisi10, Eliana Rulli10, Davide Poli10, Luciano Carlucci10, Valter Torri10, Roldano Fossati10, Elena Biagioli11. 1. European Institute of Oncology, IRCCS, Milan, Italy; University of Milan-Bicocca, Milan, Italy. 2. European Institute of Oncology, IRCCS, Milan, Italy. 3. Università Sapienza, Dipartimento Materno Infantile e Scienze Urologiche, AOU Policlinico Umberto I di Roma, Italy. 4. Istituto Oncologico Veneto IOV - IRCCS, Padova, Italy. 5. ASST Spedali Civili-Università degli Studi di Brescia, Brescia, Italy. 6. Azienda Unità Sanitaria Locale di Reggio Emilia-IRCCS, Reggio Emilia, Italy. 7. Clinica Ostetrica e Ginecologica - Ospedale S.Gerardo di Monza, Milano, Italy; University of Milan-Bicocca, Milan, Italy. 8. Department of Medicine, Ospedali Galliera, Genova, Italy. 9. European Institute of Oncology, IRCCS, Milan, Italy; Gynecologic Oncology Unit, IRCCS-Regina Elena National Cancer Institute, Rome, Italy. 10. Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Milano, Italy. 11. Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Milano, Italy. Electronic address: elena.biagioli@marionegri.it.
Abstract
BACKGROUND: Previous findings showed that cediranib-olaparib increased PFS in women with recurrent platinum-sensitive ovarian cancer compared to olaparib alone. METHODS: 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). RESULTS: 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. CONCLUSIONS: 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. CLINICAL TRIAL IDENTIFICATION: IRFMN-OVA-7289, EudraCT: 2016-003964-38, NCT03314740.
BACKGROUND: Previous findings showed that cediranib-olaparib increased PFS in women with recurrent platinum-sensitive ovarian cancer compared to olaparib alone. METHODS: 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). RESULTS: 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. CONCLUSIONS: 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. CLINICAL TRIAL IDENTIFICATION: IRFMN-OVA-7289, EudraCT: 2016-003964-38, NCT03314740.