Department of Radiation Oncology, ACTREC/TMH, Tata Memorial Centre, Homi Bhabha National Institute (HBNI), Kharghar, Navi Mumbai, India.
Clinical Research Secretariat, ACTREC/TMH, Tata Memorial Centre, Homi Bhabha National Institute (HBNI), Kharghar, Navi Mumbai, India.
Clin Oncol (R Coll Radiol). 2022 Dec;34(12):786-795. doi: 10.1016/j.clon.2022.03.009. Epub 2022 Apr 3.
Replacing cisplatin with cetuximab concurrently during radiotherapy has been one of the strategies of treatment de-escalation in human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC). However, until recently, there were limited data on the efficacy and safety of such an approach. A systematic search of the literature was carried out to identify prospective randomised controlled trials comparing definitive cisplatin-based chemoradiotherapy (CT-RT) versus cetuximab-based bioradiotherapy (BRT) in HPV-positive OPSCC. Overall survival and locoregional control were primary outcomes of interest; rates of acute and late toxicities (≥grade 3) were secondary end points. Outcome data were aggregated using a random-effects model as per Cochrane methodology including risk of bias assessment and expressed as hazard ratio or risk ratio as appropriate with respective 95% confidence intervals. Data from five randomised controlled trials involving 1560 patients with HPV-positive OPSCC were aggregated in the meta-analysis. Cetuximab-based BRT was associated with a significantly increased risk of death (hazard ratio = 2.83, 95% confidence interval 1.22-6.57; P = 0.02) and locoregional relapse (hazard ratio = 2.78, 95% confidence interval 1.77-4.39; P < 0.0001) compared with cisplatin-based CT-RT. Cisplatin was associated with higher rates of acute ≥grade 3 toxicity in terms of acute kidney injury, dry mouth, febrile neutropenia, hearing impairment, nausea and vomiting, whereas dermatitis and acneiform rash were more common with cetuximab. There were no significant differences in overall rates of late ≥grade 3 toxicity (risk ratio = 0.63, 95% confidence interval = 0.36-1.10; P = 0.10). In conclusion, there is moderate-certainty evidence that cetuximab-based BRT leads to inferior efficacy outcomes compared with cisplatin-based CT-RT in the definitive curative-intent management of HPV-associated OPSCC.
在放射治疗中同时用西妥昔单抗替代顺铂一直是 HPV 相关口咽鳞状细胞癌（OPSCC）治疗降级策略之一。然而，直到最近，这种方法的疗效和安全性的数据仍然有限。我们进行了系统的文献检索，以确定比较含顺铂的放化疗（CT-RT）与含西妥昔单抗的生物放疗法（BRT）在 HPV 阳性 OPSCC 中的前瞻性随机对照试验。总生存和局部区域控制是主要关注的结局；急性和晚期毒性（≥3 级）发生率是次要终点。根据 Cochrane 方法学，使用随机效应模型汇总结局数据，包括偏倚风险评估，并以适当的风险比或危险比以及相应的 95%置信区间表示。对纳入的 5 项随机对照试验共 1560 例 HPV 阳性 OPSCC 患者的数据进行了汇总分析。与含顺铂的 CT-RT 相比，西妥昔单抗为基础的 BRT 与死亡风险显著增加相关（危险比=2.83，95%置信区间 1.22-6.57；P=0.02）和局部区域复发（危险比=2.78，95%置信区间 1.77-4.39；P<0.0001）。顺铂与急性≥3 级毒性（急性肾损伤、口干、发热性中性粒细胞减少症、听力损伤、恶心和呕吐）的发生率较高相关，而西妥昔单抗则更常见皮炎和痤疮样皮疹。晚期≥3 级毒性的总发生率无显著差异（风险比=0.63，95%置信区间=0.36-1.10；P=0.10）。总之，有中等确定性证据表明，在 HPV 相关 OPSCC 的确定性治愈性治疗中，西妥昔单抗为基础的 BRT 导致疗效结局不如含顺铂的 CT-RT。
