M Friedlander1, J Rau2, C K Lee3, W Meier4, A Lesoin5, J-W Kim6, A Poveda7, M Buck8, G Scambia9, M Shimada10, F Hilpert11, M T King12, P Debruyne13, A Bologna14, S Malander15, B J Monk16, E Petru17, P Calvert18, T J Herzog19, C Barrett20, A du Bois21. 1. ANZGOG, Randwick, Australia; The Prince of Wales Clinical School University of New South Wales, Randwick, Australia. Electronic address: m.friedlander@unsw.edu.au. 2. Coordinating Center for Clinical Trials, Philipps University of Marburg, Marburg, Germany. 3. ANZGOG, Sydney, Australia; National Health and Medical Research Council (NHMRC) Clinical Trials Centre at The University of Sydney, Sydney, Australia. 4. AGO, Duesseldorf, Germany; Department of Gynecology and Obstetrics, Evangelisches Krankenhaus Duesseldorf, Duesseldorf, Germany. 5. GINECO, Lille, France; Department of Gynecology, Centre Oscar Lambret, Lille, France. 6. KGOG, Seoul, Republic of Korea; Department of Obstetrics and Gynecology, Seoul National University, Seoul, Republic of Korea. 7. GEICO, Valencia, Spain; Fundacion Instituto Valenciano de Oncologica, Valencia, Spain. 8. ANZGOG, Nedland, Australia; Sir Charles Gairdner Hospital, Nedland, Australia. 9. MITO, Roma, Italy; Department of Oncology, Catholic University of Sacred Heart, Roma, Italy. 10. JGOG, Nishimachi, Yonago, Japan; Department of Obstetrics and Gynecology, Tottori University School of Medicine, Nishimachi, Yonago, Japan. 11. AGO, Hamburg, Germany; Onkologisches Therapiezentrum am Krankenhaus Jerusalem, Hamburg, Germany. 12. ANZGOG, Camperdown, Australia; The University of Sydney, Camperdown, Australia. 13. BGOG, Kortrijk, Belgium; Academic Hospital Groeninge, Kortrijk, Belgium. 14. MaNGO, Reggio Emilia, Italy; IRCCS-Arcispedale Santa Maria Nuova, Oncologia Medica, Reggio Emilia, Italy. 15. NSGO, Lund, Denmark; Department of Oncology, University Hospital Lund, Lund, Denmark. 16. Gynecologic Oncology Californian Consortium, Phoenix, USA; Creighton School of Medicine at St. Joseph's Hospital Phoenix, Phoenix, USA. 17. Department of Obstetrics and Gynecology, Medical University of Graz, Graz, Austria. 18. Cancer Trials Ireland, Dublin, Ireland. 19. NYGOG, Cincinnati, USA; Barrett Cancer Center, University of Cincinnati Cancer Institute, Cincinnati, USA. 20. GlaxoSmithKline Pharmaceuticals, Uxbridge, UK. 21. AGO Germany (leading group within this GCIG consortium); Department of Gynecology & Gynecologic Oncology, Kliniken Essen Mitte, Essen, Germany.
Abstract
Background: Health-related quality of life (HRQoL) was a secondary end point in AGO-OVAR 16, which randomized 940 patients with EOC after first-line chemotherapy to maintenance pazopanib (PZ) or placebo (P). Additional post hoc analyses were carried out to investigate additional patient-centered end points. Patients and methods: HRQoL was measured with EORTC-QLQ-C30, QLQ-OV28 and EQ-5D-3L. Pre-specified end points included mean differences in HRQoL between treatment arms. Exploratory analyses included quality-adjusted progression-free survival (QAPFS), impact of specific symptoms and progressive disease (PD) on HRQoL and time to second-line chemotherapy. The objective was to provide clinical perspective to the significant median PFS gain of 5.6 months with PZ. Results: There were statistically significant differences between PZ and P in QLQ-C30 global health status [5.5 points; 95% confidence interval (CI), 0.7-10.4, P = 0.024] from baseline to 25 months, but not EQ-5D-3L (0.018 points; 95% CI - 0.033 to 0.069, P = 0.485). The impact of diarrhea was captured in QLQ-OV28 Abdominal/GI-Symptoms scale (8.1 points; 95% CI 3.6-12.5, P = 0.001). QAPFS was 386 days (95% CI 366-404 days) with PZ versus 359 days (95% CI 338-379 days) with placebo (P = 0.052). PD was associated with a decline in HRQoL (P < 0.0001). Median time to second-line chemotherapy was 19.7 months with PZ and 15.0 months with P [hazard ratio (HR) 0.72, 95% CI 0.69-0.86, P = 0.0001]. Conclusions: There were small to no significant mean score differences in global HRQoL and EQ5D-3L between PZ and placebo, respectively, despite the increased toxicity of PZ. Exploratory end points including QAPFS, impact of specific symptoms on HRQoL during treatment and at PD help place the PFS gain with PZ in context and interpret the results. Additional patient-centered end points should be considered in trials of maintenance therapy in EOC beyond mean differences in HRQoL scores alone, to support the benefit to patients of prolongation of PFS. Clinical Trials Registration Number: NCT00866697.
RCT Entities:
Background: Health-related quality of life (HRQoL) was a secondary end point in AGO-OVAR 16, which randomized 940 patients with EOC after first-line chemotherapy to maintenance pazopanib (PZ) or placebo (P). Additional post hoc analyses were carried out to investigate additional patient-centered end points. Patients and methods: HRQoL was measured with EORTC-QLQ-C30, QLQ-OV28 and EQ-5D-3L. Pre-specified end points included mean differences in HRQoL between treatment arms. Exploratory analyses included quality-adjusted progression-free survival (QAPFS), impact of specific symptoms and progressive disease (PD) on HRQoL and time to second-line chemotherapy. The objective was to provide clinical perspective to the significant median PFS gain of 5.6 months with PZ. Results: There were statistically significant differences between PZ and P in QLQ-C30 global health status [5.5 points; 95% confidence interval (CI), 0.7-10.4, P = 0.024] from baseline to 25 months, but not EQ-5D-3L (0.018 points; 95% CI - 0.033 to 0.069, P = 0.485). The impact of diarrhea was captured in QLQ-OV28 Abdominal/GI-Symptoms scale (8.1 points; 95% CI 3.6-12.5, P = 0.001). QAPFS was 386 days (95% CI 366-404 days) with PZ versus 359 days (95% CI 338-379 days) with placebo (P = 0.052). PD was associated with a decline in HRQoL (P < 0.0001). Median time to second-line chemotherapy was 19.7 months with PZ and 15.0 months with P [hazard ratio (HR) 0.72, 95% CI 0.69-0.86, P = 0.0001]. Conclusions: There were small to no significant mean score differences in global HRQoL and EQ5D-3L between PZ and placebo, respectively, despite the increased toxicity of PZ. Exploratory end points including QAPFS, impact of specific symptoms on HRQoL during treatment and at PD help place the PFS gain with PZ in context and interpret the results. Additional patient-centered end points should be considered in trials of maintenance therapy in EOC beyond mean differences in HRQoL scores alone, to support the benefit to patients of prolongation of PFS. Clinical Trials Registration Number: NCT00866697.
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Authors: Maria-Pilar Barretina-Ginesta; Bradley J Monk; Sileny Han; Bhavana Pothuri; Annika Auranen; Dana M Chase; Domenica Lorusso; Charles Anderson; Sophie Abadie-Lacourtoisie; Noelle Cloven; Elena I Braicu; Amnon Amit; Andrés Redondo; Ruchit Shah; Nehemiah Kebede; Carol Hawkes; Divya Gupta; Tatia Woodward; David M O'Malley; Antonio González-Martín Journal: Ther Adv Med Oncol Date: 2022-09-22 Impact factor: 5.485