Crook Timothy, Patil Darshana, Nagarkar Rajnish, Gaya Andrew, Plowman Nicholas, Limaye Sewanti, Srivastava Navin, Akolkar Dadasaheb, Ranade Anantbhushan, Bhatt Amit, Datta Vineet, Bose Chirantan, Apurwa Sachin, Patil Sanket, Kumar Prashant, Srinivasan Ajay, Datar Rajan
Broomfield Hospital, Chelmsford, United Kingdom.
Datar Cancer Genetics, Nasik, India.
Front Mol Med. 2021 Sep 20;1:749283. doi: 10.3389/fmmed.2021.749283. eCollection 2021.
Angiogenic factors are commonly activated in solid tumors and present a viable therapeutic target. However, anticancer treatment with angiogenesis inhibitors (AGI) is limited to a few cancers, mostly as monotherapy and not selected based on molecular indications. We aimed to determine whether patient-specific combination regimens with AGI and other anticancer agents when selected based on multi-analyte tumor interrogation (ETA: Encyclopedic Tumor Analysis) can expand the scope of AGIs in advanced refractory solid organ cancers with improved treatment responses. We evaluated treatment outcomes in 60 patients with advanced, refractory solid organ cancers who received ETA-guided combination regimens of AGI with other targeted, endocrine or cytotoxic agents. Radiological evaluation of treatment response was followed by determination of Objective Response Rate (ORR), Disease Control Rate (DCR), Progression Free Survival (PFS) and Overall Survival (OS). Among the 60 patients, Partial Response (PR) was observed in 28 cases (46.7%), Stable Disease (SD) was observed in 29 cases (48.3%) and Disease Progression (PD, within 60 days) was observed in 3 cases (5.0%). The ORR was 46.7% and DCR was 95.0%. At the most recent follow-up the median PFS (mPFS) was 5.0 months and median OS (mOS) was 8.9 months. There were no Grade 4 therapy related adverse events or treatment related deaths. ETA-guided patient-specific combination regimens with AGI and other anti-neoplastic agents, can yield improved outcomes over AGI monotherapy. Trial Registration: Details of all trials are available at WHO-ICTRP: https://apps.who.int/trialsearch/. RESILIENT ID CTRI/2018/02/011,808. LIQUID IMPACT ID CTRI/2019/02/017,548.
血管生成因子在实体瘤中通常被激活，是一个可行的治疗靶点。然而，使用血管生成抑制剂（AGI）的抗癌治疗仅限于少数几种癌症，大多作为单一疗法，且并非基于分子指标进行选择。我们旨在确定，当基于多分析物肿瘤检测（ETA：综合肿瘤分析）选择患者特异性的AGI与其他抗癌药物联合方案时，是否能扩大AGI在晚期难治性实体器官癌症中的应用范围，并改善治疗反应。我们评估了60例晚期难治性实体器官癌症患者的治疗结果，这些患者接受了ETA指导的AGI与其他靶向、内分泌或细胞毒性药物的联合方案。在对治疗反应进行影像学评估后，测定客观缓解率（ORR）、疾病控制率（DCR）、无进展生存期（PFS）和总生存期（OS）。在这60例患者中，28例（46.7%）观察到部分缓解（PR），29例（48.3%）观察到病情稳定（SD），3例（5.0%）观察到疾病进展（PD，在60天内）。ORR为46.7%，DCR为95.0%。在最近一次随访时，中位PFS（mPFS）为5.0个月，中位OS（mOS）为8.9个月。没有4级治疗相关不良事件或治疗相关死亡。ETA指导的患者特异性AGI与其他抗肿瘤药物联合方案，相比AGI单一疗法可产生更好的治疗结果。试验注册：所有试验的详细信息可在世卫组织国际临床试验注册平台查询：https://apps.who.int/trialsearch/。RESILIENT试验编号CTRI/2018/02/011,808。LIQUID IMPACT试验编号CTRI/2019/02/017,548。
