Oxaliplatin prior to PARP inhibitor in BRCA-mutated ovarian cancer

Author:

Nicoletto Maria Ornella1,Baldoni Alessandra2,Cavallin Francesco3,Grego Andrea4,Falci Cristina5,Nardin Margherita6,Mammano Enzo7,Lai Eleonora5,Torri Valter8

Affiliation:

1. Medical Oncology 2, Istituto Oncologico Veneto IRCCS, via Gattamelata 64, Padova, 35121, Italy

2. Department of Medical Oncology, AULSS 3 Serenissima, Mirano Hospital, Mirano, (VE), Italy

3. Independent statistician, Solagna (VI), Italy

4. Department of Surgery, Oncology and Gastroenterology, University of Padova, Padova, Italy

5. Medical Oncology 2, Istituto Oncologico Veneto IRCCS, Padova, Italy

6. Radiology department, Istituto Oncologico Veneto IRCCS, Padova, Italy

7. Department of Surgery, Ospedale Sant’Antonio, Padova, Italy

8. Laboratory of Methodology for Clinical Research, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Milano, Italy

Abstract

Background: The use of PARP inhibitor (PARPi) has shown a considerable benefit in progression-free survival (PFS) in relapsed, platinum-sensitive epithelial ovarian cancer (OC). Objective: Our study aimed to investigate the impact of the last platinum-based chemotherapy treatment in response to PARPi. Design: Retrospective cohort study. Patients and methods: The study involved 96 consecutive, pretreated, platinum-sensitive advanced OC patients. Demographics and clinical data were retrieved from clinical records. PFS and overall survival (OS) were calculated from the start of PARPi. Results: Germline BRCA mutation was investigated in all cases. Platinum-based chemotherapy before PARPi maintenance therapy included pegylated liposomal doxorubicin-oxaliplatin (PLD-Ox) in 46 patients (48%) and other platinum-based chemotherapy in 50 patients (52%). During a median follow-up of 22 months from the beginning of PARPi therapy, 57 patients relapsed (median PFS: 12 months) and 64 patients died (median OS: 23 months). During multivariable analysis, receiving PLD-Ox before PARPi was associated with improved PFS [hazard ratio (HR): 0.46, 95% CI: 0.26–0.82] and OS (HR: 0.48, 95% CI: 0.27–0.83). In 36 BRCA-mutated patients, PLD-Ox was associated with improved PFS (2-year PFS: 70.0% versus 25.0%, p = 0.02). Conclusion: Receiving PLD-Ox before PARPi may improve prognosis in platinum-sensitive advanced OC patients and may provide advantages in the BRCA-mutated subgroup.

Publisher

SAGE Publications

Subject

Oncology

Reference40 articles.

1. European Institute of Women’s Health. Policy brief: Women and ovarian cancer in the EU, https://eurohealth.ie/policy-brief-women-and-ovarian-cancer-in-the-eu-2018 (2018, accessed 1 March 2021).

2. null

3. I numeri del cancro in Italia, https://www.aiom.it/wp-content/uploads/2019/09/2019_Numeri_Cancro-operatori-web.pdf (2019, accessed 1 March 2021).

4. Epithelial ovarian cancer

5. Selective Inhibition of BRCA2-Deficient Mammary Tumor Cell Growth by AZD2281 and Cisplatin

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