Park Junsik, Kim Se Ik, Jeong Soo Young, Kim Yup, Bookman Michael A, Kim Jae-Weon, Kim Byoung-Gie, Lee Jung-Yun
Department of Obstetrics and Gynecology, Institute of Women's Life Medical Science, Yonsei University College of Medicine, Seoul, Republic of Korea; Severance Biomedical Science Institute, Yonsei University College of Medicine, Seoul, Republic of Korea.
Department of Obstetrics and Gynecology, Seoul National University College of Medicine, Seoul, Republic of Korea.
Gynecol Oncol. 2022 Apr;165(1):97-104. doi: 10.1016/j.ygyno.2022.02.002. Epub 2022 Feb 10.
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.
随着聚（二磷酸腺苷 - 核糖）聚合酶抑制剂（PARPi）使用的增加，PARPi耐药性对铂类耐药性存在潜在影响。SOLO2的一项事后分析表明，在接受过奥拉帕利而非安慰剂治疗的患者中，后续铂类为基础的治疗反应有所降低。本多中心、回顾性、观察性研究旨在确定奥拉帕利对复发性上皮性卵巢癌（EOC）后续治疗的影响。
收集了2012年1月至2020年6月期间在韩国三家机构接受二线铂类化疗的BRCA1/2突变肿瘤的EOC患者数据（n = 197）。二线化疗后接受奥拉帕利维持治疗的患者被分配到奥拉帕利组（n = 105），未接受奥拉帕利维持治疗的患者被分配到对照组（n = 92）。主要终点是从第二次疾病进展日期（PFS1）到第三次疾病进展日期（PFS2）的时间间隔，以PFS2 - PFS1表示。
正如预期，奥拉帕利组的PFS1长于对照组。然而，奥拉帕利组的PFS2 - PFS1显著短于对照组（中位数7.9对13.6个月；p = 0.0005）。即使将对照组中的三线PARPi维持（交叉）患者排除，奥拉帕利组对后续治疗的反应仍然较差（中位数7.7对11.5；p = 0.0422）。
与未接受奥拉帕利的对照组相比，二线化疗后在奥拉帕利维持治疗期间病情进展的铂敏感BRCA1/2突变肿瘤患者对三线化疗的反应较小，这表明对奥拉帕利的耐药性可能导致化疗耐药。
