Induction vs Adjuvant Chemoradiotherapy in Patients With High-Risk N2 to N3 Nasopharyngeal Carcinoma: A Phase 3 Randomized Clinical Trial.

Background

To compare the efficacy and safety of induction-concurrent with concurrent-adjuvant chemotherapy in high-risk N2 to N3 nasopharyngeal carcinoma.

比较诱导-同步与同步-辅助化疗在高风险N2至N3期鼻咽癌中的疗效和安全性。

DESIGN, SETTING, AND PARTICIPANTS: In this open-label, randomized, phase 3 clinical trial conducted at Sun Yat-sen University Cancer Center (China) from November 20, 2017, to March 19, 2021, patients aged 18 to 65 years with stage T1-4N2-3M0 and a pretreatment Epstein-Barr virus DNA level of 1500 or more copies/mL were enrolled.

在这项开放标签、随机、III期临床试验中，从2017年11月20日至2021年3月19日，在中山大学肿瘤中心（中国）进行，纳入了年龄在18至65岁之间，分期为T1-4N2-3M0，且治疗前Epstein-Barr病毒DNA水平为1500拷贝/毫升或以上的患者。

The data were analyzed from December 2024 to March 2025.

数据从2024年12月至2025年3月进行分析。

intervention

The patients were randomly assigned to receive 3 cycles of paclitaxel-cisplatin-fluorouracil induction chemotherapy followed by concurrent chemoradiotherapy or concurrent chemoradiotherapy followed by 3 cycles of cisplatin-fluorouracil adjuvant chemotherapy.

患者被随机分配接受3个周期的紫杉醇-顺铂-氟尿嘧啶诱导化疗，随后进行同步放化疗，或者接受同步放化疗后进行3个周期的顺铂-氟尿嘧啶辅助化疗。

main_outcome_and_measure

The primary end point was 3-year progression-free survival, assessed locally by the investigator and defined as the time from random assignment to documented local or regional relapse, distant metastasis, or death of any cause, whichever occurred first.

主要终点是3年无进展生存期，由研究者在本地评估，并定义为从随机分配到记录的局部或区域复发、远处转移或任何原因导致的死亡中的任何一种情况首次发生的时间。

Results

A total of 162 patients (median [IQR] age, 44 [34-53] years; 40 female individuals [24.7%]) were assigned to the induction-concurrent group and 162 (median [IQR] age, 45 [37-52] years; 36 female individuals [22.2%]) to the concurrent-adjuvant group.

在研究中，共有162名患者（中位年龄[四分位数间距]，44[34-53]岁；女性40名[24.7%]）被分配到诱导-同步组，另外162名患者（中位年龄[四分位数间距]，45[37-52]岁；女性36名[22.2%]）被分配到同步-辅助组。

Regarding the data cutoff (October 8, 2024), the median (IQR) follow-up period was 60.4 (58.2-62.6) months.

关于数据截止日期（2024年10月8日），中位随访期为60.4（58.2-62.6）个月。

The 3-year progression-free survivalrates were 73.5% (95% CI, 65.9%-79.6%) in the induction-concurrent group and 70.4% (95% CI, 62.7%-76.8%) in the concurrent-adjuvant group (stratified hazard ratio, 0.86; 95% CI, 0.58-1.27; P = .45).

诱导-同步组的3年无进展生存率为73.5%（95%置信区间，65.9%-79.6%），而同步-辅助组为70.4%（95%置信区间，62.7%-76.8%）（分层风险比，0.86；95%置信区间，0.58-1.27；P = .45）。

The most common short-term grade 3 or worse adverse events were leukopenia (53 of 160 [33.1%] in the induction-concurrent group vs 47 of 142 [33.1%] in the concurrent-adjuvant group), neutropenia (52 [32.5%] vs 32 [22.5%], respectively), and mucositis (47 [29.4%] vs 42 [29.6%], respectively).

最常见的短期3级或更严重的不良事件是白细胞减少症（诱导-同步组160例中有53例[33.1%]，而同步-辅助组142例中有47例[33.1%]），中性粒细胞减少症（分别有52例[32.5%]和32例[22.5%]），以及黏膜炎（分别有47例[29.4%]和42例[29.6%]）。

The most common grade 3 or worse late adverse eventwas auditory or hearing loss (10 [6.3%] vs 12 [8.5%], respectively).

最常见的3级或更严重的晚期不良事件是听觉或听力损失（分别有10例[6.3%]和12例[8.5%]）。

Two patients in the induction-concurrent group died of treatment-related toxic effects.

诱导-同时治疗组中有2名患者因治疗相关的毒性效应死亡。

No treatment-related death occurred in the concurrent-adjuvant group.

在同时辅助治疗组中没有发生与治疗相关的死亡。

conclusions_and_relevance

This randomized clinical trial found that induction-concurrent chemotherapy did not significantly improve progression-free survivalcompared with concurrent-adjuvant chemotherapy in high-risk N2 to N3 nasopharyngeal carcinoma.

这项随机临床试验发现，在高风险N2至N3期鼻咽癌患者中，诱导-同时化疗与同时辅助化疗相比，并没有显著改善无进展生存期。

Both treatment strategies were effective, and clinicians should discuss with the patients about the potential risks and benefits of the induction chemotherapy or adjuvant chemotherapy to provide the most appropriate treatment for patients with high-risk features.

两种治疗策略均有效，临床医生应与患者讨论诱导化疗或辅助化疗的潜在风险和益处，为具有高风险特征的患者提供最合适的治疗。

trial_registration

ClinicalTrials.gov Identifier: NCT03306121.

ClinicalTrials.gov 注册号：NCT03306121。