Stephenson Cancer Center Section of Gynecologic Oncology, University of Oklahoma Health Sciences Center; Oklahoma City, OK, USA.
Division of Gynecologic Oncology, University of Virginia, Department of Obstetrics and Gynecology; Charlottesville, VA, USA.
Gynecol Oncol. 2022 Jul;166(1):44-49. doi: 10.1016/j.ygyno.2022.04.016. Epub 2022 Apr 28.
The aim of this study was to examine the tolerability and efficacy of combination bevacizumab rucaparib therapy in patients with recurrent cervical or endometrial cancer.
PATIENTS & METHODS: Thirty-three patients with recurrent cervical or endometrial cancer were enrolled. Patients were required to have tumor progression after first line treatment for metastatic, or recurrent disease. Rucaparib was given at 600 mg BID twice daily for each 21-day cycle. Bevacizumab was given at 15 mg/kg on day 1 of each 21-day cycle. The primary endpoint was efficacy as determined by objective response rate or 6-month progression free survival.
Of the 33 patients enrolled, 28 were evaluable. Patients with endometrial cancer had a response rate of 17% while patients with cervical cancer had a response rate of 14%. Median progression free survival was 3.8 months (95% C·I 2.5 to 5.7 months), and median overall survival was 10.1 months (95% C·I 7.0 to 15.1 months). Patients with ARID1A mutations displayed a better response rate (33%) and 6-month progression free survival (PFS6) rate (67%) than the entire study population. Observed toxicity was similar to that of previous studies with bevacizumab and rucaparib.
The combination of bevacizumab with rucaparib did not show significantly increased anti-tumor activity in all patients with recurrent cervical or endometrial cancer. However, patients with ARID1A mutations had a higher response rate and PFS6 suggesting this subgroup may benefit from the combination of bevacizumab and rucaparib. Further study is needed to confirm this observation. No new safety signals were seen.
本研究旨在评估贝伐珠单抗联合鲁卡帕利治疗复发性宫颈癌或子宫内膜癌患者的耐受性和疗效。
纳入 33 例复发性宫颈癌或子宫内膜癌患者。患者需在转移性或复发性疾病的一线治疗后发生肿瘤进展。鲁卡帕利每日两次、每次 600mg 给药，每 21 天为一个周期。贝伐珠单抗在每个 21 天周期的第 1 天给予 15mg/kg。主要终点是根据客观缓解率或 6 个月无进展生存期来评估疗效。
33 例患者中，28 例可评估。子宫内膜癌患者的缓解率为 17%，宫颈癌患者的缓解率为 14%。中位无进展生存期为 3.8 个月（95%CI：2.5 至 5.7 个月），中位总生存期为 10.1 个月（95%CI：7.0 至 15.1 个月）。与整个研究人群相比，存在 ARID1A 突变的患者显示出更好的缓解率（33%）和 6 个月无进展生存率（PFS6，67%）。观察到的毒性与贝伐珠单抗和鲁卡帕利的既往研究相似。
在所有复发性宫颈癌或子宫内膜癌患者中，贝伐珠单抗联合鲁卡帕利并未显示出明显增加的抗肿瘤活性。然而，存在 ARID1A 突变的患者缓解率和 PFS6 更高，这表明这一亚组可能受益于贝伐珠单抗联合鲁卡帕利治疗。需要进一步的研究来证实这一观察结果。未观察到新的安全性信号。
