Son Ji, Lin Heather Y, Fu Siqing, Biter Amadeo B, Dumbrava Ecaterina E, Karp Daniel D, Naing Aung, Pant Shubham, Piha-Paul Sarina A, Rodon Jordi, Subbiah Vivek, Tsimberidou Apostolia M, Yap Timothy A, Frumovitz Michael M, Jazaeri Amir A, Ramirez Pedro T, Westin Shannon N, Yuan Ying, Meric-Bernstam Funda, Hong David S
Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
J Immunother Precis Oncol. 2023 Jan 6;6(1):10-18. doi: 10.36401/JIPO-22-23. eCollection 2023 Feb.
We aimed to identify clinical, pathologic, and treatment factors that are predictive of response and survival in patients with cervical cancer referred to phase I clinical trials.
Patients with cervical cancer who received at least one dose of a phase I investigational agent at our institution between 2014 and 2022 were included. The log-rank test was used to analyze differences in progression-free survival (PFS) and overall survival (OS), and multivariable regression analysis was performed.
We included 65 patients with a median age of 41 years (range, 20-74), 3 prior therapies (range, 1-7), and 67.7% squamous carcinoma. The rate of distant metastasis at trial entry was 84.6%. The most common molecular alterations included PIK3CA (46.5%), PD-L1+ (46.2%), EPH (30.0%), and CREBBP (23.1%); 23.1% had received a prior checkpoint inhibitor. Phase I trials were for immunotherapy (58.5%) or targeted therapy (41.5%). The rate of biomarker matching was 21.5%. For all patients, median PFS was 3.6 months (95% CI, 2.0-5.2) and OS was 9.3 months (95% CI, 7.0-10.6). Factors at study entry associated with worse survival were presence of bone metastasis (PFS 1.6 vs 4.4 months: hazard ratio [HR], 2.8; = 0.001; OS 3.8 vs 10.0 months: HR, 3.9; < 0.0001) and absolute lymphocyte count below 1000/μL (PFS 1.8 vs 5.2 months: HR, 2.9; = 0.0004; OS 7.0 vs 10.6 months: HR, 3.2; = 0.0009). Factors associated only with worse OS were absolute neutrophil count above 4700/μL, hemoglobin below 10.5 g/dL, and smoking status. Grade 3+ treatment-related adverse events were seen in 16.9% of cases.
Bone metastasis and absolute lymphocyte count below normal range at phase I study entry portend poor survival in patients with recurrent or metastatic cervical cancer.
我们旨在确定可预测转诊至I期临床试验的宫颈癌患者的反应和生存情况的临床、病理及治疗因素。
纳入2014年至2022年间在我们机构接受至少一剂I期研究药物的宫颈癌患者。采用对数秩检验分析无进展生存期（PFS）和总生存期（OS）的差异，并进行多变量回归分析。
我们纳入了65例患者，中位年龄41岁（范围20 - 74岁），既往接受过3种治疗（范围1 - 7种），67.7%为鳞状细胞癌。试验入组时远处转移率为84.6%。最常见的分子改变包括PIK3CA（46.5%）、PD-L1阳性（46.2%）、EPH（30.0%）和CREBBP（23.1%）；23.1%的患者曾接受过检查点抑制剂治疗。I期试验为免疫治疗（58.5%）或靶向治疗（41.5%）。生物标志物匹配率为21.5%。所有患者的中位PFS为3.6个月（95%CI，2.0 - 5.2），OS为9.3个月（95%CI，7.0 - 10.6）。研究入组时与较差生存相关的因素为骨转移的存在（PFS 1.6个月对4.4个月：风险比[HR]，2.8；P = 0.001；OS 3.8个月对10.0个月：HR，3.9；P < 0.0001）以及绝对淋巴细胞计数低于1000/μL（PFS 1.8个月对5.2个月：HR，2.9；P = 0.0004；OS 7.0个月对10.6个月：HR，3.2；P = 0.0009）。仅与较差OS相关的因素为绝对中性粒细胞计数高于4700/μL、血红蛋白低于10.5 g/dL以及吸烟状态。16.9%的病例出现3级及以上治疗相关不良事件。
I期研究入组时存在骨转移和绝对淋巴细胞计数低于正常范围预示着复发或转移性宫颈癌患者生存较差。
