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Abstract CT163: KEYNOTE-412: Pembrolizumab plus chemoradiation vs chemoradiation alone for locally advanced head and neck squamous cell carcinoma

Background: Chemoradiation (CRT) with cisplatin is the standard of care for patients with locally advanced head and neck squamous cell carcinoma (LA-HNSCC) not treated by surgery. Preclinical data in murine cancer models show improved tumor growth control and survival when radiation therapy (RT) is combined with a PD-1 inhibitor. Pembrolizumab is effective for treatment of recurrent/metastatic HNSCC, and initial results from a phase 1b study suggest that pembrolizumab plus CRT is tolerable in patients with LA-HNSCC. KEYNOTE-412 (NCT03040999) is a phase 3, randomized, placebo-controlled, double-blind trial to determine the efficacy and safety of pembrolizumab given with CRT and as maintenance therapy versus placebo plus CRT in LA-HNSCC. Trial design: Patients will be randomly assigned (1:1) to receive pembrolizumab 200 mg every 3 weeks plus cisplatin-based CRT or placebo plus cisplatin-based CRT. Treatment will be stratified by RT regimen (accelerated RT [56-70 Gy, 6 fractions/week for 6 weeks] or standard RT [56-70 Gy, 5 fractions/week for 7 weeks]), tumor site/p16 status (oropharynx p16 positive vs p16 negative or larynx/hypopharynx/oral cavity), and disease stage (III vs IV). A priming dose of pembrolizumab or placebo will be given 1 week before CRT, followed by 2 doses during CRT and an additional 14 doses after CRT, for a total of 17 pembrolizumab or placebo infusions. Eligibility criteria include age ≥18 years; newly diagnosed, treatment-naive, oropharyngeal p16 positive (any T4 or N3), oropharyngeal p16 negative (any T3-T4 or N2a-N3), or larynx/hypopharynx/oral cavity (any T3-T4 or N2a-N3) SCC; evaluable tumor burden (RECIST v1.1); and ECOG performance status 0-1. Treatment will be discontinued at centrally confirmed disease progression, unacceptable toxicity, or patient/physician decision to withdraw. Response will be assessed by computed tomography or magnetic resonance imaging 12 weeks after CRT, every 3 months for 3 years, then every 6 months for years 4 and 5. Patients will be evaluated to determine the necessity of neck dissection 12 weeks after completion of CRT; neck dissection will be recommended in cases of persistent disease. After a patient experiences disease progression or starts new anticancer therapy, the patient will begin survival follow-up and will be contacted every 3 months during years 1 through 3 and every 6 months during years 4 and 5 until death, withdrawal of consent, or the end of the study, whichever occurs first. Safety will be monitored throughout the study and for 30 days after treatment end. The primary end point is event-free survival. Secondary end points include overall survival, safety, and patient-reported outcomes. Recruitment is ongoing in 21 countries and will continue until ~780 patients are enrolled. Citation Format: Lillian L. Siu, Lisa Licitra, Yun Gan Tao, Chia-Jui Yen, Danny Rischin, John Waldron, Barbara Burtness, Vincent Gregoire, Sanjiv Agarwala, Jeffrey Yorio, Jean-Pierre DeLord, Sercan Aksoy, Sadakatsu Ikeda, Ruey-Long Hong, Joy Yang Ge, Holly Brown, Behzad Bidadi, Jean-Pascal Machiels. KEYNOTE-412: Pembrolizumab plus chemoradiation vs chemoradiation alone for locally advanced head and neck squamous cell carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr CT163.