Second-line olaparib maintenance therapy is associated with poor response to subsequent chemotherapy in BRCA1/2-mutated epithelial ovarian cancer: A multicentre retrospective study

• Published in: Gynecologic oncology Vol. 165; no. 1; pp. 97 - 104
• Main Authors: Park, Junsik, Kim, Se Ik, Jeong, Soo Young, Kim, Yup, Bookman, Michael A., Kim, Jae-Weon, Kim, Byoung-Gie, Lee, Jung-Yun
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.04.2022
• Subjects: BRCA1 Protein - genetics; BRCA2 Protein - genetics; Carcinoma; Carcinoma, Ovarian Epithelial - drug therapy; Carcinoma, Ovarian Epithelial - genetics; Disease Progression; Female; Hematology, Oncology, and Palliative Medicine; Humans; Maintenance Chemotherapy; Mutation; Neoplasm Recurrence, Local - drug therapy; Obstetrics and Gynecology; Olaparib; Ovarian Epithelial; Ovarian neoplasms; Ovarian Neoplasms - drug therapy; Ovarian Neoplasms - genetics; Ovarian Neoplasms - pathology; Phthalazines; Piperazines; Poly(ADP-ribose) Polymerase Inhibitors - pharmacology; Poly(ADP-ribose) Polymerase Inhibitors - therapeutic use; Poly(ADP-ribose) Polymerases; Prognosis; Recurrence; Retrospective Studies; Survival; Recurrence; Carcinoma; Prognosis; Ovarian neoplasms; Ovarian Epithelial; Olaparib; Survival
• ISSN: 0090-8258; 1095-6859; 1095-6859
• DOI: 10.1016/j.ygyno.2022.02.002

With expanded use of poly (adenosine diphosphate-ribose) polymerase inhibitors (PARPi), there is a potential impact of PARPi resistance on platinum resistance. A post-hoc analysis of SOLO2 demonstrated a reduction in response to subsequent platinum-based therapy among patients who received prior olaparib but not placebo. The present multicentre, retrospective, observational study was conducted to determine the effects of olaparib on subsequent therapy for recurrent epithelial ovarian cancer (EOC). Data on EOC patients with BRCA1/2-mutated tumours who received second-line platinum-based chemotherapy between January 2012 and June 2020, at three South Korean institutions (n = 197) were collected. Patients who received olaparib as maintenance therapy after second-line chemotherapy were assigned to the olaparib group (n = 105), and subjects who did not receive olaparib maintenance therapy were assigned to the control group (n = 92). The primary endpoint was time intervals from the date of second disease progression (PFS1) to the date of third disease progression (PFS2), expressed as PFS2 − PFS1. As expected, PFS1 in the olaparib group was longer than the control group. However, PFS2 – PFS1 in the olaparib group was significantly shorter than that of the control group (median 7.9 vs. 13.6 m; p = 0.0005). Even when the third-line PARPi maintenance (cross-over) patients were excluded from the control group, the response to subsequent therapy in the olaparib group remained poor (median 7.7 vs. 11.5; p = 0.0422). Patients with platinum-sensitive BRCA1/2 mutated tumours who progressed during olaparib maintenance after second-line chemotherapy were less likely to respond to third-line chemotherapy compared to controls who did not receive olaparib, suggesting that resistance to olaparib may contribute to chemotherapy resistance. •Although second-line olaparib significantly improved PFS1, olaparib did not prolong PFS2.•Relapsed patients despite 2 L-olaparib maintenance show poor response to subsequent chemotherapy.•The negative effects were more pronounced in patients with PFS1 > 12 months.