尼妥珠单抗-顺铂-放疗与顺铂-放疗治疗人乳头瘤病毒阴性口咽癌的对比
Nimotuzumab-cisplatin-radiation versus cisplatin-radiation in HPV negative oropharyngeal cancer.
作者信息
Noronha Vanita, Patil Vijay Maruti, Joshi Amit, Mahimkar Manoj, Patel Usha, Pandey Manish Kumar, Chandrasekharan Arun, Dsouza Hollis, Bhattacharjee Atanu, Mahajan Abhishek, Sabale Nilesh, Agarwal Jai Prakash, Ghosh-Laskar Sarbani, Budrukkar Ashwini, D'Cruz Anil K, Chaturvedi Pankaj, Pai Prathamesh S, Chaukar Devendra, Nair Sudhir, Thiagarajan Shivakumar, Banavali Shripad, Prabhash Kumar
机构信息
Department of Medical Oncology, Tata Memorial Hospital, HBNI, Mumbai, India.
These authors contributed equally to this work.
出版信息
Oncotarget. 2020 Jan 28;11(4):399-408. doi: 10.18632/oncotarget.27443.
BACKGROUND
Addition of nimotuzumab to weekly cisplatin and radiation improves outcomes in head and neck cancer. HPV negative oropharyngeal cancer has unsatisfactory treatment outcomes and is a candidate for escalation of treatment. We wanted to determine whether the addition of nimotuzumab to cisplatin-radiation could improve outcomes in these poor-risk tumors.
METHODS
This was a subgroup analysis of a phase 3 randomized study. In this study, locally advanced head and neck cancer patients undergoing definitive chemoradiation were randomly allocated to weekly cisplatin (30 mg/m2 IV)- radiation (66-70 Gy) {CRT arm} or nimotuzumab (200 mg weekly) -weekly cisplatin (30 mg/m2)-radiation (66-70 Gy) {NCRT arm}. The data of HPV negative oropharyngeal cancer was extracted from the database of this study for the analysis. HPV testing was done with p16 immunohistochemistry (IHC) staining and reported according to the CAP criteria. The outcomes assessed were progression-free survival (PFS), disease-free survival (DFS), locoregional control, and overall survival (OS). Interaction test was performed between the study arms and HPV status prior to doing any HPV specific analysis for each of the studied outcomes. Kaplan Meier estimates for 2 year OS with 95%CI was calculated. The hazard ratio was obtained using COX regression analysis.
RESULTS
We had 187 HPV negative oropharyngeal cancers, 91 in the CRT arm and 96 in NCRT arm. The interaction test was significant for PFS ( = 0.000), locoregional control ( = 0.007) and overall survival ( = 0.002) but not for DFS ( = 0.072). The 2- year PFS was 31.5% (95%CI 21.5-42) in CRT arm versus 57.2% (95%CI 45.8-67.1) in NCRT arm (HR -0.54; 95%CI 0.36-0.79, = 0.002). The 2-year LRC was 41.4% (95%CI 29.8-52.6) in the CRT arm versus in 60.4% (95%CI 48.7-70.2) in the NCRT arm (HR -0.61; 95%CI 0.4-0.94, = 0.024). The addition of nimotuzumab also lead to an improvement in 2-year OS from 39.0% (95%CI 28.4-49.6) to 57.6% (95%CI 46.3-67.4) (HR-0.63, 95%CI 0.43-0.92, = 0.018).
CONCLUSIONS
The addition of nimotuzumab to weekly cisplatin-radiation improves outcomes inclusive of OS in HPV negative oropharyngeal cancers.
背景
在每周顺铂和放疗基础上加用尼妥珠单抗可改善头颈癌的治疗效果。人乳头瘤病毒（HPV）阴性的口咽癌治疗效果不理想，是治疗升级的候选对象。我们想确定在顺铂-放疗基础上加用尼妥珠单抗是否能改善这些高危肿瘤的治疗效果。
方法
这是一项3期随机研究的亚组分析。在该研究中，接受根治性放化疗的局部晚期头颈癌患者被随机分配至每周顺铂（30mg/m²静脉注射）-放疗（66 - 70Gy）组{CRT组}或尼妥珠单抗（每周200mg）-每周顺铂（30mg/m²）-放疗（66 - 70Gy）组{NCRT组}。从本研究数据库中提取HPV阴性口咽癌的数据进行分析。HPV检测采用p16免疫组化（IHC）染色，并根据美国病理学家学会（CAP）标准报告。评估的结局指标为无进展生存期（PFS）、无病生存期（DFS）、局部区域控制和总生存期（OS）。在对每个研究结局进行任何HPV特异性分析之前，在研究组和HPV状态之间进行交互检验。计算2年OS的Kaplan Meier估计值及95%置信区间（CI）。使用COX回归分析获得风险比。
结果
我们有187例HPV阴性口咽癌患者，CRT组91例，NCRT组96例。交互检验在PFS（P = 0.000）、局部区域控制（P = 0.007）和总生存期（P = 0.002）方面有显著意义，但在DFS方面无显著意义（P = 0.072）。CRT组2年PFS为31.5%（95%CI 21.5 - 42），而NCRT组为57.2%（95%CI 45.8 - 67.1）（风险比 -0.54；95%CI 0.36 - 0.79，P = 0.002）。CRT组2年局部区域控制率为41.4%（95%CI 29.8 - 52.6），NCRT组为60.4%（95%CI 48.7 - 70.2）（风险比 -0.61；95%CI 0.4 - 0.94，P = 0.024）。加用尼妥珠单抗还使2年总生存期从39.0%（95%CI 28.4 - 49.6）提高到57.6%（95%CI 46.3 - 67.4）（风险比 -0.63，95%CI 0.43 - 0.92，P = 0.018）。
结论
在每周顺铂-放疗基础上加用尼妥珠单抗可改善HPV阴性口咽癌包括总生存期在内的治疗效果。
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