Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, United States of America.
Department of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX, United States of America.
Gynecol Oncol. 2018 Dec;151(3):407-413. doi: 10.1016/j.ygyno.2018.10.008. Epub 2018 Oct 24.
To describe the clinical outcomes associated with the use of checkpoint inhibitor therapy in recurrent ovarian malignancy.
Women with recurrent ovarian cancer treated with an immune checkpoint inhibitor between 1/2012 and 8/2017 were included. RECIST criteria determined disease status, and immune related adverse events (irAE) were graded per trial protocols. Predictors of response, irAE, progression free survival (PFS) and overall survival (OS) were investigated.
Forty-four women were included with a median age of 53 years, median of 4 prior lines of chemotherapy, and most commonly high grade serous pathology (59.1%). 3 patients had partial response and 3 had pseudoprogression, for a response rate of 14.2%. In subset analysis of high grade serous (HGSOC) pathology, platinum sensitivity at time of checkpoint inhibitor therapy was correlated with response (p = 0.01). There were 28 grade 3/4 irAEs in 21 patients (47.7%). Combination therapy rather than monotherapy predicted irAE (OR 5.7, CI 1.6-20.9, p = 0.02). The most common severe irAE was elevation in hepatic or pancreatic enzymes in 12 total patients (13.6% each). Interestingly, the number of genes mutated was protective from hepatic/pancreatic AE (p = 0.02).
While response rate was similar to prior literature, in patients with HGSOC platinum sensitivity at time of checkpoint inhibitor initiation was correlated to response. Grade 3/4 hepatic and pancreatic enzyme elevations were more common in ovarian cancer patients than has been previously reported in other tumor types. The number of genes mutated was inversely correlated to risk of this type of irAEs but not to total irAEs.
描述在复发性卵巢恶性肿瘤中使用检查点抑制剂治疗的临床结果。
纳入了 2012 年 1 月至 2017 年 8 月期间接受免疫检查点抑制剂治疗的复发性卵巢癌女性患者。根据 RECIST 标准确定疾病状态，并根据试验方案对免疫相关不良反应 (irAE) 进行分级。研究了反应、irAE、无进展生存期 (PFS) 和总生存期 (OS) 的预测因素。
共纳入 44 例患者，中位年龄为 53 岁，中位化疗次数为 4 次，最常见的病理类型为高级别浆液性肿瘤 (59.1%)。3 例患者有部分缓解，3 例有假性进展，反应率为 14.2%。在高级别浆液性卵巢癌 (HGSOC) 病理的亚组分析中，检查点抑制剂治疗时的铂类敏感性与反应相关 (p=0.01)。有 21 例患者 (47.7%) 出现 28 例 3/4 级 irAE。联合治疗而非单药治疗预测 irAE (OR 5.7，95%CI 1.6-20.9，p=0.02)。最常见的严重 irAE 是 12 例患者中各有 13.6%的肝或胰腺酶升高。有趣的是，突变基因的数量对肝/胰腺 AE 有保护作用 (p=0.02)。
尽管反应率与既往文献相似，但在 HGSOC 患者中，检查点抑制剂起始时的铂类敏感性与反应相关。卵巢癌患者的 3/4 级肝酶和胰腺酶升高比其他肿瘤类型更为常见。突变基因的数量与这种类型的 irAE 的风险呈反比，但与总 irAE 无关。
