Induction Nivolumab Before Chemoradiation in High-Risk Human Papillomavirus-Driven Oropharynx Cancers: IMMUNEBOOST-HPV, a Multicenter Randomized Phase II Trial.

Induction immunotherapy before chemoradiation (CRT) may improve outcomes.

在放化疗（CRT）前进行诱导免疫治疗可能改善治疗结果。

This randomized phase II trial assessed the feasibility and safety of induction nivolumab before CRT in this high-risk population.

这项随机II期试验评估了在放化疗前使用诱导纳武单抗在这一高风险人群中的可行性和安全性。

Methods

Eligible patients had HPV-positive OPC with either T4 and/or N2/N3 disease or a smoking history >10 pack-years.

符合条件的患者为HPV阳性口咽癌，伴有T4和/或N2/N3期疾病，或有超过10包年的吸烟史。

Patients were randomly assigned 1:2 to receive either standard CRT (70 Gy with cisplatin, control arm [CA], n = 20) or two infusions of nivolumab followed by CRT (experimental arm [EA], n = 41).

患者按1:2的比例随机分配接受标准放化疗（70 Gy 加顺铂，对照组[CA]，n=20）或接受两次纳武利尤单抗输注后进行放化疗（实验组[EA]，n=41）。

The primary end point was the rate of patients who received full treatment in due time (FTDT), defined as (1) two nivolumab infusions on days 1 and 13-17, (2) CRT started between days 27-37 after the first nivolumab infusion, (3) no radiotherapy break ≥7 days, (4) >95% of theoretical/prescribed RT dose, and (5) cisplatin dose received ≥200 mg/m2.

主要终点是按时完成全部治疗的患者比例（FTDT），定义为：（1）在第1天和第13-17天接受两次纳武利尤单抗输注，（2）在第一次纳武利尤单抗输注后的第27-37天开始放化疗，（3）无超过7天的放疗中断，（4）实际/处方放疗剂量>95%，以及（5）接受的顺铂剂量≥200 mg/m2。

If two patients or less in the EA failed FTDT, the strategy would be considered feasible.

如果EA组中有两个或更少的患者在FTDT中失败，该策略将被认为是可行的。

Secondary end points included oncologic outcomes and toxicity.

次要终点包括肿瘤学结果和毒性。

Results

Between July 2019 and September 2021, 62 patients were randomly assigned.

在2019年7月至2021年9月期间，共有62名患者被随机分配。

Median follow-up was 37.5 months.

中位随访时间为37.5个月。

The primary end point was not met: four of 41 patients in EA received <200 mg/m2 cisplatin.

主要终点未达成：41名EA患者中有4名接受了不到200 mg/m2的顺铂。

Grade 4 to 5 acute adverse events occurred only in EA, in seven patients.

仅在EA组中发生了4级到5级的急性不良事件，涉及七名患者。

The 2-year cumulative incidence(95% CI) of relapse was 7.3% (1.9 to 18.0) in EA versus 15.0% (3.6 to 34.0) in CA.

EA组2年累积复发发生率（95%置信区间）为7.3%（1.9至18.0），而CA组为15.0%（3.6至34.0）。

Conclusions

Induction nivolumab before CRT did not meet the predefined feasibility threshold because of reduced cisplatin dosing after toxicity in 10% of patients.

在CRT前使用诱导性nivolumab未达到预定的可行性阈值，因为有10%的患者在毒性后减少了顺铂剂量。

The relapse incidencewas numerically lower in the EA but this finding is exploratory and requires confirmation.

复发发生率在EA组中数值上较低，但这一发现是探索性的，需要进一步确认。