Haddad Robert, Fayette Jérôme, Teixeira Maria, Prabhash Kumar, Mesia Ricard, Kawecki Andrzej, Dechaphunkul Arunee, Dinis José, Guo Ye, Masuda Muneyuki, Hsieh Ching-Yun, Ghi Maria Grazia, Vaz de Melo Sette Claudia, Harrington Kevin, Tahara Makoto, Saba Nabil F, Lau Agnes, Jiang Tao, Yan Yibing, Ballinger Marcus, Kaul Monika, Matheny Christina, Cuchelkar Vaikunth, Wong Deborah J
Dana-Farber Cancer Institute, Boston, Massachusetts.
Centre Leon Berard, Département d'Hématologie et d'Oncologie, Lyon, France.
JAMA. 2025 May 13;333(18):1599-1607. doi: 10.1001/jama.2025.1483.
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.
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.
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.
The primary end point was investigator-assessed event-free survival. Other end points included overall survival and safety.
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.
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.
ClinicalTrials.gov Identifier: NCT03452137.
治疗局部晚期头颈部鳞状细胞癌（LA SCCHN）涉及手术、放疗和化疗的任何组合，随后进行局部复发或远处转移的常规监测。鉴于患者预后较差，改善治疗方案的重大临床需求仍未得到满足。
评估阿替利珠单抗维持治疗对多模式确定性治疗后疾病进展风险高的LA SCCHN患者的疗效和安全性。
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（临床截止日期：2023年9月27日）期间，在23个国家的128个地点招募患者。符合条件的患者患有LA SCCHN（IVa/IVb期，累及口腔、喉、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[美国癌症联合委员会癌症分期手册，第八版]），在多模式确定性治疗后无疾病进展。
患者按1:1随机分组，每3周接受一次1200mg阿替利珠单抗或安慰剂治疗，持续1年，或直至疾病复发、疾病进展、出现不可接受的毒性或撤回同意书。
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。
总体而言，406例患者被随机分配接受阿替利珠单抗（n = 203）或安慰剂（n = 203）治疗；两个治疗组的基线人口统计学特征均衡（<65岁，分别为142例[70.0%]对155例[76.4%]；男性，分别为168例[82.8%]对174例[85.7%]；亚洲人，分别为68例[35.6%]对61例[31.0%]；黑人，均为1例[0.5%]；白人，分别为121例[63.4%]对135例[68.5%]）。在临床截止时（中位随访46.5个月），研究者评估的阿替利珠单抗组中位无事件生存期为59.5个月（95%CI，46.8至不可估计），安慰剂组为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 = 0.68）。阿替利珠单抗组和安慰剂组的总生存期无差异（24个月总生存率分别为82.0%和79.2%）。未发现新的或意外的安全信号。
在本研究中，阿替利珠单抗并未改善多模式确定性治疗后疾病进展风险高的LA SCCHN患者的临床结局。这些数据为检查点抑制剂在这种疾病背景下全球人群中的有限活性提供了证据。总体而言，免疫疗法对LA SCCHN患者的作用仍有待确定。
ClinicalTrials.gov标识符：NCT03452137。
