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. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03452137.