Sinha Shubhadeep D, Biswas Ghanashyam, Bheemareddy Bala Reddy, Chary Sreenivasa, Thakur Pankaj, Jain Minish, Maksud Tanveer, Pawar Suraj, Chatterjee Koushik, Voonna Murali Krishna, Goel Anil, Puligundla Krishna Chaitanya, Lakshmaiah Kuntegowdanahalli Chinnagiriyappa, Talluri Leela, Vattipalli Ramya, Kakkunnath Sheejith
Department of Clinical Development & Medical Affairs, Hetero, Hyderabad, Telangana, India.
Department of Medical Oncology, Sparsh Hospital & Critical Care, Bhubaneshwar, Odisha, India.
Cancer Inform. 2023 Jun 1;22:11769351231177277. doi: 10.1177/11769351231177277. eCollection 2023.
The aim of this study was to evaluate the post-marketing safety, tolerability, immunogenicity and efficacy of Bevacizumab (manufactured by Hetero Biopharma) in a broader population of patients with solid tumors.
This phase IV, prospective, multi-centric clinical study was carried out in Indian patients with solid malignancies (metastatic colorectal cancer, non-squamous non-small-cell lung cancer, metastatic renal cell carcinoma) treated with Bevacizumab between April 2018 and July 2019. This study included 203 patients from 16 tertiary care oncology centers across India for safety assessment, of which a subset of 115 patients who have consented were also evaluated for efficacy and immunogenicity. This study was prospectively registered in the Clinical Trial Registry of India (CTRI), and was commenced only after receiving approval from the competent authority (Central Drugs Standard Control Organization, CDSCO).
Out of the 203 enrolled patients, 121 (59.6%) patients reported 338 adverse events (AEs) during this study. Of 338 reported AEs, 14 serious adverse events (SAEs) were reported by 13 patients including 6 fatal SAEs, assessed as unrelated to the study medication and 7 non-fatal SAEs, 5 assessed as related, and 3 unrelated to Bevacizumab. Most AEs reported in this study (33.9%) were general disorders and administration site conditions, followed by gastrointestinal disorders (29.1%). The most frequently reported AEs were diarrhea (11.3%), asthenia (10.3%), headache (8.9%), pain (7.4%), vomiting (7.9%), and neutropenia (5.9%). At the end of the study, 2 (1.75%) of 69 patients reported antibodies to Bevacizumab without affecting safety and efficacy. However, at the end of 12 months, no patient had reported antibodies to Bevacizumab. Complete response (CR), partial response (PR), stable disease (SD), and progressive disease (PD) were reported in 18.3%, 22.6%, 9.6%, and 8.7% of patients, respectively. The overall response rate (CR + PR) was reported in 40.9% of patients at the end of the study. Disease control rate (DCR), also known as the clinical benefit rate (CBR) was reported in 50.4% of patients.
Bevacizumab (Cizumab, Hetero Biopharma) was observed to be safe, well tolerated, lacking immunogenicity, and efficacious in the treatment of solid tumors. The findings of this phase IV study of Bevacizumab, primarily as a combination therapy regimen suggest its suitability and rationality for usage in multiple solid malignancies.
CTRI/2018/4/13371 [Registered on CTRI http://ctri.nic.in/Clinicaltrials/advsearch.php : 19/04/2018]; Trial Registered Prospectively.
本研究旨在评估贝伐单抗（由海特生物制药公司生产）在更广泛的实体瘤患者群体中的上市后安全性、耐受性、免疫原性和疗效。
本IV期前瞻性多中心临床研究于2018年4月至2019年7月期间，在接受贝伐单抗治疗的印度实体恶性肿瘤患者（转移性结直肠癌、非鳞状非小细胞肺癌、转移性肾细胞癌）中开展。本研究纳入了来自印度16家三级肿瘤护理中心的203例患者进行安全性评估，其中115例同意参与研究的患者子集还进行了疗效和免疫原性评估。本研究已在印度临床试验注册中心（CTRI）进行前瞻性注册，且仅在获得主管当局（中央药品标准控制组织，CDSCO）批准后才开始。
在203例入组患者中，121例（59.6%）患者在本研究期间报告了338例不良事件（AE）。在报告的338例AE中，13例患者报告了14例严重不良事件（SAE），其中包括6例致命SAE，评估为与研究药物无关，7例非致命SAE，5例评估为相关，3例与贝伐单抗无关。本研究中报告的大多数AE（33.9%）为一般疾病和给药部位情况，其次是胃肠道疾病（29.1%）。最常报告的AE为腹泻（11.3%）、乏力（10.3%）、头痛（8.9%）、疼痛（7.4%）、呕吐（7.9%）和中性粒细胞减少（5.9%）。在研究结束时，69例患者中有2例（1.75%）报告了针对贝伐单抗的抗体，但未影响安全性和疗效。然而，在12个月结束时，没有患者报告针对贝伐单抗的抗体。分别有18.3%、22.6%、9.6%和8.7%的患者报告了完全缓解（CR）、部分缓解（PR）、疾病稳定（SD）和疾病进展（PD）。在研究结束时，40.9%的患者报告了总缓解率（CR + PR）。疾病控制率（DCR），也称为临床获益率（CBR），在50.4%的患者中报告。
观察到贝伐单抗（西izumab，海特生物制药公司）在实体瘤治疗中安全、耐受性良好、缺乏免疫原性且有效。贝伐单抗的本IV期研究结果，主要作为联合治疗方案，表明其在多种实体恶性肿瘤中的使用具有适用性和合理性。
CTRI/2018/4/13371 [于CTRI http://ctri.nic.in/Clinicaltrials/advsearch.php注册：2018年4月19日]；前瞻性注册试验。
