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Clinical Trial
. 2025 May 13;333(18):1599-1607.
doi: 10.1001/jama.2025.1483.

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

Robert Haddad  1 , Jérôme Fayette  2 , Maria Teixeira  3 , Kumar Prabhash  4 , Ricard Mesia  5 , Andrzej Kawecki  6 , Arunee Dechaphunkul  7 , José Dinis  8 , Ye Guo  9 , Muneyuki Masuda  10 , Ching-Yun Hsieh  11 , Maria Grazia Ghi  12 , Claudia Vaz de Melo Sette  13 , Kevin Harrington  14 , Makoto Tahara  15 , Nabil F Saba  16 , Agnes Lau  17 , Tao Jiang  17 , Yibing Yan  17 , Marcus Ballinger  17 , Monika Kaul  17 , Christina Matheny  17 , Vaikunth Cuchelkar  17 , Deborah J Wong  18
Affiliations
Clinical Trial

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

Robert Haddad et al. JAMA. .

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.

Trial registration: ClinicalTrials.gov Identifier: NCT03452137.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Haddad reported grants from Genentech during the conduct of the study; advisory board fees from EMD Serono, PDS, Genmab, Rapt Therapeutics, AstraZeneca, Bayer, and Exelexis; serving on the data and safety monitoring board for Nanobiotix, PSI, Hookipa, and Boehringer Ingelheim; consulting outside the submitted work; serving as National Comprehensive Cancer Network panel chair; and being a member of the Head and Neck Cancer Panel. Dr Fayette reported advisory board fees from AstraZeneca, Meru, MSD, Roche, and BMS during the conduct of the study; and fees for serving as principal investigator from Pfizer and Takeda outside the submitted work. Dr Mesia reported support for attending meetings from Merck and MSD. Dr Kawecki reported honoraria from MSD, BMS, and Merck outside the submitted work. Dr Masuda reported consulting or advisory roles for Abbott Japan and serving on a speakers bureau for Abbott Japan outside the submitted work. Dr Vaz de Melo Sette reported fees from Johnson & Johnson for serving on an advisory board, lectures, and travel expenses; fees from Daiishi Sankyo for travel expenses and lectures; fees from AstraZeneca for serving on an advisory board and for lectures; and fees from Boehringer Ingelheim for travel expenses outside the submitted work. Dr Harrington reported grants from AstraZeneca and Boehringer Ingelheim; fees from MSD and EMD Serono to his institute; and grants from Replimune during the conduct of the study. Dr Tahara reported honoraria from Eisai, MSD, Bayer, Ono Pharma, Novartis, and Lilly outside the submitted work. Dr Saba reported advisory roles for AstraZeneca, Eisai Medical, Exelixis, Merck, EMD Serono, Pfizer, Kura, Vaccinex, CUE, BioNTech, GSK, TOSK, Seagen, Flamingo, Infinity, Inovio, Aveo, Medscape, Onclive, UpToDate, BMS, Cornerstone, Celldex, Surface Oncology Astex, Imugene, Faron Pharmaceutical, Coherus, Adagene, Fulgent Springer, Nanobiotix, and Taiho; and funding from Exelixis and BMS. Dr Lau reported nonfinancial support from Ashfield MedComms during the conduct of the study. Dr Yan reported employment by and stock in Roche outside the submitted work. Dr Ballinger reported employment by and stock in Genentech during the conduct of the study and employment by and stock in Genentech outside the submitted work. Dr Kaul reported employment by and stock in Genentech outside the submitted work. Dr Matheny reported employment by Roche and Genentech. Dr Cuchelkar reported employment by Genentech during the conduct of the study and outside the submitted work. Dr Wong reported grants from Genentech paid to her institution during the conduct of the study; grants from Bicara Therapeutics, AstraZeneca, Hookipa, BioNTech, Flamingo, and Gilead; consulting or advisory fees from Merck; grants from Bristol Myers Squibb, invoX, Top Alliance, Pfizer, Regeneron, Eli Lilly, GSK, and Sensei Bio outside the submitted work; and consulting fees from Rapt Therapeutics and Coherus outside the submitted work. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Recruitment, Randomization, and Follow-Up in the IMvoke010 Trial
Figure 2.
Figure 2.. Kaplan-Meier Curves for Investigator-Assessed Event-Free Survival and Overall Survival
The median entries refer to the time at which 50% of the subjects had experienced an event of interest or were censored. The minimum follow-up (vertical dashed line) was 43 months and was defined at the study level as the duration between the “last patient in” date (February 14, 2020) and the clinical cutoff date (September 27, 2023). HR indicates hazard ratio; NE, not estimable.
See this image and copyright information in PMC

Comment in

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