2025年3月13日出版的《美国医学会杂志》发表了加州科学家的一项最新研究成果。来自基因泰克的Deborah J. Wong课题组提出了Atezolizumab治疗高危局部晚期头颈部鳞状细胞癌。

重要性:治疗局部晚期头颈部鳞状细胞癌（LA SCCHN）包括手术、放疗和化疗的任何组合，随后常规监测局部复发或远处转移。鉴于患者预后不佳，改善治疗方案的临床需求仍未得到满足。

目的:评估在多模式最终治疗后疾病进展高风险的LA SCCHN患者中维持atezolizumab的疗效和安全性。

设计、设置和参与者：IMvoke010是一项3期、全球、双盲、随机临床试验。2018年4月3日至2020年2月14日期间，在23个国家的128个地点招募了患者（临床截止日期：2023年9月27日）。符合条件的患者患有LA SCCHN (IVa/IVb期，包括口腔、喉部、下咽或人乳头瘤病毒阴性口咽，或III期人乳头瘤病毒阳性口咽[AJCC癌症分期手册，第八版])，经多模式最终治疗后无疾病进展。患者被随机（1:1）每3周接受atezolizumab 1200mg或安慰剂治疗，持续1年或直到疾病复发、疾病进展、不可接受的毒性或同意退出。

主要成果和措施：主要终点是研究者评估的无事件生存期。其他终点包括总生存期和安全性。

结果:总体而言，406名患者被随机分配接受atezolizumab （n= 203）或安慰剂（n= 203）；两个治疗组的基线人口统计学平衡(65岁，142[70.0%]对155 [76.4%]；男性168人（82.8%）vs 174人（85.7%）；亚洲人，68人（35.6%）vs 61人（31.0%）；黑色，1 [0.5%]vs 1 [0.5%]；White， 121人（63.4%）vs 135人（68.5%）。在临床截止点（中位随访，46.5个月），研究者评估的中位无事件生存期为阿特唑单抗组59.5个月（95% CI， 46.8至不可估计），安慰剂组52.7个月（95% CI， 41.4至不可估计）(风险比，0.94；95% ci, 0.70-1.26；P = .68点)。atezolizumab和安慰剂的总生存期无差异（24个月总生存期分别为82.0%和79.2%）。没有发现新的或意外的安全信号。

研究结果表明，在这项研究中，atezolizumab并没有改善LA SCCHN患者在多模式最终治疗后疾病进展高风险的临床结果。这些数据有助于证明检查点抑制剂在这种疾病背景下的全球人群中活性有限。总的来说，免疫治疗在LA SCCHN患者中的作用仍有待确定。

附：英文原文

Title: Atezolizumab in High-Risk Locally Advanced Squamous Cell Carcinoma of the Head and Neck: A Randomized Clinical Trial

Author: Robert Haddad, Jérme Fayette, Maria Teixeira, Kumar Prabhash, Ricard Mesia, Andrzej Kawecki, Arunee Dechaphunkul, José Dinis, Ye Guo, Muneyuki Masuda, Ching-Yun Hsieh, Maria Grazia Ghi, Claudia Vaz de Melo Sette, Kevin Harrington, Makoto Tahara, Nabil F. Saba, Agnes Lau, Tao Jiang, Yibing Yan, Marcus Ballinger, Monika Kaul, Christina Matheny, Vaikunth Cuchelkar, Deborah J. Wong

Issue&Volume: 2025-03-13

Abstract: Importance  Treating locally advanced squamous cell carcinoma of the head and neck (LA SCCHN) involves any combination of surgery, radiation, and chemotherapy, followed by routine monitoring for local recurrence or distant metastases. Given the poor patient outcomes, a significant unmet clinical need for improved treatment options remains.

Objective  To evaluate efficacy and safety of maintenance atezolizumab in patients with LA SCCHN at high risk of disease progression after multimodal definitive treatment.

Design, Setting, and Participants  IMvoke010 was a phase 3, global, double-blind, randomized clinical trial. Patients were recruited at 128 sites in 23 countries between April 3, 2018, and February 14, 2020 (clinical cutoff date: September 27, 2023). Eligible patients had LA SCCHN (stage IVa/IVb involving the oral cavity, larynx, hypopharynx, or human papillomavirus–negative oropharynx, or stage III human papillomavirus–positive oropharynx [AJCC Cancer Staging Manual, eighth edition]) without disease progression after multimodal definitive treatment.

Intervention  Patients were randomized (1:1) to receive atezolizumab 1200 mg or placebo every 3 weeks for 1 year or until disease recurrence, disease progression, unacceptable toxicity, or consent withdrawal.

Main Outcomes and Measures  The primary end point was investigator-assessed event-free survival. Other end points included overall survival and safety.

Results  Overall, 406 patients were randomized to receive atezolizumab (n=203) or placebo (n=203); baseline demographics were balanced between both treatment groups (<65 years, 142 [70.0%] vs 155 [76.4%]; male, 168 [82.8%] vs 174 [85.7%]; Asian, 68 [35.6%] vs 61 [31.0%]; Black, 1 [0.5%] vs 1 [0.5%]; and White, 121 [63.4%] vs 135 [68.5%], respectively). At clinical cutoff (median follow-up, 46.5 months), median investigator-assessed event-free survival was 59.5 months (95% CI, 46.8 to not estimable) with atezolizumab vs 52.7 months (95% CI, 41.4 to not estimable) with placebo (hazard ratio, 0.94; 95% CI, 0.70-1.26; P=.68). There was no difference in overall survival between atezolizumab and placebo (24-month overall survival, 82.0% vs 79.2%, respectively). No new or unexpected safety signals were identified.

Conclusions and Relevance  In this study, atezolizumab did not improve clinical outcomes in patients with LA SCCHN at high risk of disease progression after multimodal definitive treatment. These data contribute to evidence on the limited activity of checkpoint inhibitors in the global population of this disease setting. Overall, the role of immunotherapy for patients with LA SCCHN remains to be determined.

DOI: 10.1001/jama.2025.1483

Source: https://jamanetwork.com/journals/jama/fullarticle/2831624