Kristina Lindemann1, Bo Gao2, Cristina Mapagu3, Sian Fereday4, Catherine Emmanuel3, Kathryn Alsop4, Nadia Traficante4, Paul R Harnett5, David D L Bowtell6, Anna deFazio7. 1. Department of Gynaecological Oncology, Division of Cancer Medicine, Oslo University Hospital, Oslo, Norway; Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway; Crown Princess Mary Cancer Care Centre, Westmead Hospital, Sydney, New South Wales, Australia. Electronic address: klinde@ous-hf.no. 2. Crown Princess Mary Cancer Care Centre, Westmead Hospital, Sydney, New South Wales, Australia; Centre for Cancer Research, The Westmead Institute for Medical Research, Sydney, New South Wales, Australia. 3. Centre for Cancer Research, The Westmead Institute for Medical Research, Sydney, New South Wales, Australia; The University of Sydney, Sydney, New South Wales, Australia; Department of Gynaecological Oncology, Westmead Hospital, Westmead, New South Wales, Australia. 4. Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia. 5. Crown Princess Mary Cancer Care Centre, Westmead Hospital, Sydney, New South Wales, Australia; Centre for Cancer Research, The Westmead Institute for Medical Research, Sydney, New South Wales, Australia; The University of Sydney, Sydney, New South Wales, Australia. 6. Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia; Sir Peter MacCallum Department of Oncology, The University of Melbourne, Victoria, Australia; Department of Pathology, University of Melbourne, Victoria, Australia; Kinghorn Cancer Centre, Garvan Institute for Medical Research, Darlinghurst, New South Wales, Australia; Department of Biochemistry and Molecular Biology, The University of Melbourne, Victoria, Australia. 7. Centre for Cancer Research, The Westmead Institute for Medical Research, Sydney, New South Wales, Australia; The University of Sydney, Sydney, New South Wales, Australia; Department of Gynaecological Oncology, Westmead Hospital, Westmead, New South Wales, Australia. Electronic address: anna.defazio@sydney.edu.au.
Abstract
OBJECTIVE: The aim of this study was to compare response rates and survival in women with "platinum resistant" epithelial ovarian cancer (EOC) who received further platinum-based or non‑platinum chemotherapy for treatment at first relapse. METHODS: Patients with high-grade EOC (including fallopian tube and peritoneal cancer) of all histologies recruited to the Australian Ovarian Cancer Study (AOCS) and treated with platinum-based primary chemotherapy were included. Response to second-line chemotherapy, overall survival (OS) and survival after treatment for first progression (OS2) were determined in all histologies and separately in women with high-grade serous tumors. RESULTS: Of the 341 patients classified as platinum-resistant by the 6-month threshold, 243 (71%) were treated with chemotherapy at relapse. CA-125 response rates to platinum-based chemotherapy were significantly higher compared to non‑platinum chemotherapy (51% vs 21%, P < 0.001). Among patients with a platinum-free interval (PFI) of 3-6 months, OS2 in patients treated with platinum was significantly longer compared to individuals receiving non‑platinum-based treatment (median 17.67 months, 95% CI: 14.79-20.75 vs. 10.62 months, 95% CI: 8.02-12.72, P = 0.022). The patterns were similar when restricted to patients with high-grade serous histology. In patients with PFI <3 months, there was no significant difference in response or survival according to type of second-line treatment. CONCLUSIONS: Our findings further question the use of a 6-month PFI as an arbitrary threshold for subsequent treatment decision-making. Some patients considered "platinum resistant" still derive clinical benefit from platinum-based chemotherapy. Biomarkers of platinum sensitivity are needed in clinical practice to identify potential responders who should be offered re-treatment with platinum.
OBJECTIVE: The aim of this study was to compare response rates and survival in women with "platinum resistant" epithelial ovarian cancer (EOC) who received further platinum-based or non‑platinum chemotherapy for treatment at first relapse. METHODS:Patients with high-grade EOC (including fallopian tube and peritoneal cancer) of all histologies recruited to the Australian Ovarian Cancer Study (AOCS) and treated with platinum-based primary chemotherapy were included. Response to second-line chemotherapy, overall survival (OS) and survival after treatment for first progression (OS2) were determined in all histologies and separately in women with high-grade serous tumors. RESULTS: Of the 341 patients classified as platinum-resistant by the 6-month threshold, 243 (71%) were treated with chemotherapy at relapse. CA-125 response rates to platinum-based chemotherapy were significantly higher compared to non‑platinum chemotherapy (51% vs 21%, P < 0.001). Among patients with a platinum-free interval (PFI) of 3-6 months, OS2 in patients treated with platinum was significantly longer compared to individuals receiving non‑platinum-based treatment (median 17.67 months, 95% CI: 14.79-20.75 vs. 10.62 months, 95% CI: 8.02-12.72, P = 0.022). The patterns were similar when restricted to patients with high-grade serous histology. In patients with PFI <3 months, there was no significant difference in response or survival according to type of second-line treatment. CONCLUSIONS: Our findings further question the use of a 6-month PFI as an arbitrary threshold for subsequent treatment decision-making. Some patients considered "platinum resistant" still derive clinical benefit from platinum-based chemotherapy. Biomarkers of platinum sensitivity are needed in clinical practice to identify potential responders who should be offered re-treatment with platinum.
Authors: Judith E den Ouden; Guido J R Zaman; Jelle Dylus; Antoon M van Doornmalen; Winfried R Mulder; Yvonne Grobben; Wilhelmina E van Riel; Joanne A de Hullu; Rogier C Buijsman; Anne M van Altena Journal: Oncotarget Date: 2020-12-08
Authors: John B Liao; William R Gwin; Renata R Urban; Katie M Hitchcock-Bernhardt; Andrew L Coveler; Doreen M Higgins; Jennifer S Childs; Hania N Shakalia; Ron E Swensen; Sasha E Stanton; Anna V Tinker; Tanya A Wahl; Richard G Ancheta; Kathryn F McGonigle; James Y Dai; Mary L Disis; Barbara A Goff Journal: J Immunother Cancer Date: 2021-09 Impact factor: 13.751