Publication

The impact of olaparib dose reduction and treatment interruption on treatment outcome in the SOLO2/ENGOT-ov21 platinum-sensitive recurrent ovarian cancer

Francis, K. E.
; 
Kim, S. I.
; 
Friedlander, M.
; 
Gebski, V.
; 
Coquard, I. R.
; 
Clamp, A.
; 
Penson, R. T.
; 
Oza, A.
; 
Perri, T.
; 
Huzarski, T.
... show 10 more
Citations
Altmetric:
Abstract
Background Maintenance treatment with poly (ADP-ribose) polymerase (PARP) inhibitor is now the standard of care in patients with BRCA mutated platinum-sensitive recurrent ovarian cancer following response to chemotherapy. In the SOLO2 trial, adverse event (AE) associated olaparib interruption, dose reduction, and discontinuation occurred in 50%, 28%, and 17% of patients, respectively. We used data from SOLO2 trial to evaluate the impact of dose alterations on survival outcomes and identified baseline characteristics associated with dose alteration. Patients and methods We computed relative dose intensity (RDI) defined as received dose as a percentage of the standard dose (300mg twice a day) during the first twelve weeks on treatment. Patients were categorized into RDI >98%, RDI 90-98% and RDI < 90%. The association between RDI categories with progression-free survival (PFS) and overall survival (OS) were examined using a 12-week landmark Cox regression analysis. Logistic regression analysis was used to correlate baseline factors with RDI at 12-weeks. Results In patients on olaparib included in the landmark analysis (n = 185) the mean 12-week RDI was 91.4%. There was no significant difference across 12-week RDI >98% (n = 110), 90-98% (n = 29), and <90% (n = 45) categories for PFS (median, 14.2 vs. 19.3 vs. 34.4 months; P=.37) and OS (median, 49.7 vs. 49.5 vs. 54.1 months; P=.84). Risk of RDI ≤90% increased with baseline performance status 1 (OR: 2.54; 95% CI: 1.11-5.82) any nausea (OR: 3.17; 95% CI: 0.9-11.23) and with body weight ≤ 70kg (OR: 1.86; 95% CI: 0.92-3.76). Conclusions Dose reduction and interruption for the management of olaparib associated AE during the first 12 weeks did not impact on PFS and OS. When counselling patients requiring dose reductions or interruptions due to AEs, the results of this study will help assure patients that their outcomes will not be adversely affected.
Authors
Francis, K. E.
Kim, S. I.
Friedlander, M.
Gebski, V.
Coquard, I. R.
Clamp, A.
Penson, R. T.
Oza, A.
Perri, T.
Huzarski, T.
Martin-Lorente, C.
Cecere, S. C.
Colombo, N.
Ataseven, B.
Fujiwara, K.
Sonke, G.
Vergote, I.
Pujade-Lauraine, E.
Kim, J. W.
Lee, C. K.
Affiliation
National Health and Medical Research Council Clinical Trials Centre, The University of Sydney, Sydney, NSW 2050, Australia; Department of Medical Oncology, St George Hospital, Kogarah, NSW 2217, Australia. Electronic address: katherine.francis@sydney.edu.au. Seoul National University Hospital, Seoul, Korea. Prince of Wales Clinical School, UNSW and Department of Medical Oncology, Prince of Wales Hospital, Randwick, NSW 2031, Australia. National Health and Medical Research Council Clinical Trials Centre, The University of Sydney, Sydney, NSW 2050, Australia. ARCAGY-GINECO, France; Centre Léon Bérard, Lyon, France. The Christie NHS Foundation Trust and University of Manchester. Harvard Medical School, Massachusetts General Hospital, Boston, MA, USA. Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, Toronto, ON, CA. Gynecologic Oncology department, Sheba Medical hospital, Israel. Department of Genetics and Pathology, Pomeranian Medical University, 71-252 Szczecin, Poland ; Read-Gene SA, Westpomerania, 72-003 Grzepnica, Poland. Hospital Universitario de la Santa Creu i Sant Pau and GEICO. Department of uro-gynecology, Division of experimental uro-gynecological oncology, National Cancer Intitute IRCCS Fondazione 'G.Pascale' Via Mariano Semmola, 80130, Naples, Italy. Università Milano-Bicocca, Direttore Programma Ginecologia, Istituto Europeo Oncologia. Department of Gynecology and Gynecologic Oncology, Evang. Kliniken Essen-Mitte, Essen, Germany; Department of Obstetrics and Gynecology, University Hospital, LMU Munich, Germany. Department of Gynecologic Oncology, Saitama Medical University International Medical Center, Saitama, Japan. The Dutch Gynecological Oncology Group (DGOG); Department of Medical Oncology, Netherlands Cancer Institute, 1066 CX Amsterdam, the Netherlands. Belgium and Luxembourg Gynaecological Oncology Group (BGOG); Department of Oncology, KU Leuven - University of Leuven, B-3000 Leuven, Belgium. ARCAGY-GINECO, France; Université Paris Descartes, Paris, France. National Health and Medical Research Council Clinical Trials Centre, The University of Sydney, Sydney, NSW 2050, Australia; Department of Medical Oncology, St George Hospital, Kogarah, NSW 2217, Australia.
Description
Date
2022
Publisher
Collections
All Christie Publications
Show all metadata
Keywords
Type
Article
Citation
Francis KE, Kim SI, Friedlander M, Gebski V, Coquard IR, Clamp A, et al. The impact of olaparib dose reduction and treatment interruption on treatment outcome in the SOLO2/ENGOT-ov21 platinum-sensitive recurrent ovarian cancer [Internet]. Annals of Oncology. Elsevier BV; 2022.
Journal Title
Journal ISSN
Volume Title
URI
http://hdl.handle.net/10541/625113
Embedded videos