Department of Obstetrics and Gynecology, Division of General Gynecology and Gynecologic Oncology, Medical University of Vienna, 1090 Vienna, Austria.
Department of Pathology, Medical University of Vienna, 1090 Vienna, Austria.
Biomolecules. 2021 Nov 16;11(11):1700. doi: 10.3390/biom11111700.
Despite increasing clinical interest in adapting checkpoint inhibitor (CPI) therapies for patients with gynecologic malignancies, no accurate clinical biomarkers to predict therapy response and prognosis are currently available. Therefore, we aimed to assess the predictive and prognostic value of pretherapeutic body mass index (BMI) for recurrent gynecologic cancer patients as previously validated for other solid tumors. We evaluated patients with programmed cell death ligand 1 (PD-L1) positive and, in endometrial cancer, also mismatch repair deficient (MMR) gynecologic malignancies, who received the PD-1 inhibitor pembrolizumab as monotherapy (200 mg fixed-dose q3 w) from 2017 to 2020 (n = 48). Thirty-six patients receiving at least four courses were included in the final analysis. Associations between a BMI increase per 5 kg/m and overall response rate (ORR; complete + partial response), disease control rate (DCR; ORR + stable disease), progression-free (PFS), and overall survival (OS) were assessed. An elevated BMI was univariately associated with ORR (OR 10.93 [CI 2.39-49.82], = 0.002), DCR (OR 2.19 [CI 0.99-4.83], = 0.048), prolonged PFS (HR 1.54 [CI 1.03-2.34], = 0.038), and OS (HR 1.87 [CI 1.07-3.29], = 0.028). All results could be confirmed in the multivariate analyses. Pretherapeutic BMI therefore appears to be a promising readily available biomarker to identify patients with PD-L1-positive and/or MMR-deficient gynecologic malignancies who could particularly benefit from CPI treatment.
尽管人们越来越关注将检查点抑制剂 (CPI) 疗法用于妇科恶性肿瘤患者，但目前尚无准确的临床生物标志物来预测治疗反应和预后。因此，我们旨在评估治疗前体质量指数 (BMI) 对复发性妇科癌症患者的预测和预后价值，这与先前已验证的其他实体瘤结果一致。我们评估了程序性细胞死亡配体 1 (PD-L1) 阳性和子宫内膜癌中错配修复缺陷 (MMR) 妇科恶性肿瘤患者，他们在 2017 年至 2020 年间接受了 PD-1 抑制剂 pembrolizumab 单药治疗（每 3 周 200mg 固定剂量）（n = 48）。最终分析纳入了至少接受 4 个疗程的 36 名患者。评估了 BMI 每增加 5kg/m 与总缓解率（完全缓解+部分缓解，ORR）、疾病控制率（ORR+疾病稳定，DCR）、无进展生存期（PFS）和总生存期（OS）之间的关系。单因素分析显示，BMI 升高与 ORR（OR 10.93 [CI 2.39-49.82]， = 0.002）、DCR（OR 2.19 [CI 0.99-4.83]， = 0.048）、延长 PFS（HR 1.54 [CI 1.03-2.34]， = 0.038）和 OS（HR 1.87 [CI 1.07-3.29]， = 0.028）相关。多因素分析也得到了相似的结果。因此，治疗前 BMI 似乎是一种很有前途的、易于获得的生物标志物，可以识别出 PD-L1 阳性和/或 MMR 缺陷的妇科恶性肿瘤患者，他们可能特别受益于 CPI 治疗。
