Glynn Shannon M, Gaillard Stephanie, Stone Rebecca L, Fader Amanda N, Beavis Anna L
Kelly Gynecologic Oncology Service, Department of Gynecology and Obstetrics, Johns Hopkins Hospital, 600 N Wolfe St, Baltimore, MD 21287.
Gynecol Oncol Rep. 2024 Apr 2;53:101374. doi: 10.1016/j.gore.2024.101374. eCollection 2024 Jun.
Treatment for recurrent ovarian clear cell carcinoma (OCCC) is clinically challenging as response rates to traditional chemotherapy are low, and recurrence rates are high. Immunotherapy has shown promise for this ovarian cancer (OC) subtype, and tumor molecular testing allows for the identification of a patient population that might benefit most from this treatment. We describe the clinical course and somatic genomic testing of 4 patients who received pembrolizumab for recurrent OCCC concurrent with a combination of bevacizumab and/or cyclophosphamide.
All patients with OCCC treated with immune checkpoint inhibitors (ICI) within a single health system between 2018 and 2023 (excluding those on clinical trials) were identified via retrospective chart review.
Four patients were included. The average age at diagnosis was 56.5 years, and the number of prior treatments ranged from 1 to 6. All patients received pembrolizumab combined with either bevacizumab and/or cyclophosphamide. All patients (n = 3) who received pembrolizumab and bevacizumab experienced a partial response. Responses were durable, ranging from 6 to 15 months. Somatic genomic testing results demonstrated microsatellite stability and low tumor mutational burden in all patient tumors, and 3 had AT-Rich Interaction Domain 1A gene (ARID1A) mutations. Notably, two patients had treatment-limiting toxicities, one with presumed immune-mediated grade 2 myocarditis, and another with grade 5 hepatitis.
Pembrolizumab, combined with bevacizumab and cyclophosphamide, is a promising treatment option for patients with recurrent OCCC, though careful risk assessment and counseling regarding toxicities is necessary to maximize the safety and efficacy of this treatment regimen. Prospective studies are needed for validation.
复发性卵巢透明细胞癌（OCCC）的治疗在临床上具有挑战性，因为对传统化疗的反应率较低，且复发率较高。免疫疗法已显示出对这种卵巢癌（OC）亚型有前景，而肿瘤分子检测有助于识别可能从该治疗中获益最大的患者群体。我们描述了4例接受派姆单抗治疗复发性OCCC并联合贝伐单抗和/或环磷酰胺的患者的临床病程和体细胞基因组检测情况。
通过回顾性病历审查，确定了2018年至2023年期间在单一医疗系统内接受免疫检查点抑制剂（ICI）治疗的所有OCCC患者（不包括参加临床试验的患者）。
纳入4例患者。诊断时的平均年龄为56.5岁，既往治疗次数为1至6次。所有患者均接受派姆单抗联合贝伐单抗和/或环磷酰胺治疗。所有接受派姆单抗和贝伐单抗治疗的患者（n = 3）均出现部分缓解。缓解持续时间为6至15个月。体细胞基因组检测结果显示，所有患者肿瘤均为微卫星稳定且肿瘤突变负荷低，3例患者存在富含AT的相互作用结构域1A基因（ARID1A）突变。值得注意的是，2例患者出现了限制治疗的毒性反应，1例疑似免疫介导的2级心肌炎，另1例为5级肝炎。
派姆单抗联合贝伐单抗和环磷酰胺是复发性OCCC患者的一种有前景的治疗选择，不过为了使该治疗方案的安全性和有效性最大化，需要对毒性进行仔细的风险评估和咨询。需要进行前瞻性研究以进行验证。
