Study of Pembrolizumab (MK-3475) or Placebo With Chemoradiation in Participants With Locally Advanced Head and Neck Squamous Cell Carcinoma (MK-3475-412/KEYNOTE-412)

EFS was defined as the time from date of randomization to the date of first record of any of the following events: death due to any cause; progression per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) by blinded independent central review (BICR) or biopsy as indicated for locoregional progression or recurrence or distant metastasis. As well as the first record of the following types of surgery: salvage surgery for persistent or residual disease at the primary tumor site requiring surgical removal when invasive cancer is present on final pathology; neck dissection or surgery (performed for clinical or radiological disease progression per RECIST 1.1) ≤ 20 weeks from end of CRT when invasive cancer is present; or neck dissection or surgery \>20 weeks from end of CRT when invasive cancer is present. The non-parametric Kaplan-Meier method was used to estimate the EFS curve in each treatment group.

Time frame: Up to approximately 62 months

Population: All randomized participants based on the treatment group to which they were randomized.

The EORTC QLQ-C30 is a 30-item questionnaire developed to assess the quality of life (QoL) of cancer patients. For Global Health Status (GHS) (Item 29), participants are asked How would you rate your overall health during the past week? Individual items are scored on a 7-point (1=very poor to 7=excellent). Raw scores for each scale are standardized into a range of 0 to 100 by linear transformation, with a higher score indicating a better level of function and better overall GHS. A change from baseline of 10 points on the 100-point EORTC QLQ-C30 scale is considered as clinically relevant. Analysis based on a constrained longitudinal data analysis (cLDA) model with the patient reported outcomes (PRO) scores as the response variable with covariates for treatment, time, treatment by time interaction, and stratification factors of human papilloma virus (HPV) status and overall cancer stage.

Time frame: Baseline and up to week 45

Population: Participants with at least one patient reported outcome (PRO) assessment available for this specific endpoint and who had received at least 1 dose of study intervention.

The EORTC QLQ-C30 is a 30-item questionnaire developed to assess the quality of life (QoL) of cancer patients. Participant responded to 5 questions from the EORTC QLQ-C30 about their physical functioning scored on a 4-point scale (1=Not at All to 4=Very Much). Using linear transformation, raw scores were standardized, so that scores range from 0 to 100, where a higher score indicates a better physical functioning. A change from baseline of 10 points on the 100-point scale is considered as clinically relevant. Analysis was based on a cLDA model with the PRO scores as the response variable with covariates for treatment, time, treatment by time interaction, and stratification factors of HPV status and overall cancer stage.

Time frame: Baseline and up to Week 45

Population: Participants with at least one PRO assessment available for this specific endpoint and who had received at least 1 dose of study intervention.

EORTC QLQ Head and Neck Questionnaire (H&N35) measures QoL in head and Neck Cancer (HNC) patients. It consists of 7 multi-item scales (pain in the mouth, problems with swallowing, senses, speech, social eating, social contact, and sexuality). Participant responses to the pain scale (Items 31-34) were scored on a 4-point scale (1=Not at all to 4=Very much). Raw scores were standardized by linear transformation so that scores ranged from 0 to 100, with a higher score indicating more problems. Change from baseline in pain symptoms was measured. A change from baseline of 10 points on the 100-point EORTC QLQ-H&N35 is considered as clinically relevant. Analysis based on a cLDA model with the PRO scores as the response variable with covariates for treatment, time, treatment by time interaction, and stratification factors of HPV status and overall cancer stage.

Time frame: Baseline and up to Week 45

Population: Participants with at least one PRO assessment available for this specific endpoint and who had received at least 1 dose of study intervention.

EORTC QLQ Head and Neck Questionnaire (H&N35) measures QoL in head and neck cancer (HNC) patients. It consists of 7 multi-item scales (pain in the mouth, problems with swallowing, senses, speech, social eating, social contact, and sexuality). Participant responses to the speech scale (Items 30-32) were scored on a 4-point scale (1=Not at all to 4=Very much). Raw scores were standardized by linear transformation so that scores ranged from 0 to 100, with a higher score indicating more problems. Change from baseline in speech was measured. A change from baseline of 10 points on the 100-point EORTC QLQ-H&N35 is considered as clinically relevant. Analysis based on a cLDA model with the PRO scores as the response variable with covariates for treatment, time, treatment by time interaction, and stratification factors of HPV status and overall cancer stage.

Time frame: Baseline and up to Week 45

Population: Participants with at least one PRO assessment available for this specific endpoint and who had received at least 1 dose of study intervention.

EORTC QLQ Head and Neck Questionnaire (H&N35) measures QoL in head and neck cancer (HNC) patients. It consists of 7 multi-item scales (pain in the mouth, problems with swallowing, senses, speech, social eating, social contact, and sexuality). Participant responses to the swallowing scale (Items 35-38) were scored on a 4-point scale (1=Not at all to 4=Very much). Raw scores were standardized by linear transformation so that scores ranged from 0 to 100, with a higher score indicating more problems. Change from baseline in swallowing was measured. A change from baseline of 10 points on the 100-point EORTC QLQ-H&N35 is considered as clinically relevant. Analysis based on a cLDA model with the PRO scores as the response variable with covariates for treatment, time, treatment by time interaction, and stratification factors of HPV status and overall cancer stage.

Time frame: Baseline and up to Week 45

Population: Participants with at least one PRO assessment available for this specific endpoint and who had received at least 1 dose of study intervention.

An AE was defined as any untoward medical occurrence in a participant administered study drug and which does not necessarily have to have a causal relationship with the study drug. An AE is any sign, symptom, disease, or worsening of preexisting condition temporally associated with study therapy and irrespective of causality to study therapy. The number of participants who discontinued study drug due to an AE is presented.

Time frame: Up to approximately 15 months

Population: All randomized participants who received at least one dose of study treatment.

An AE was defined as any untoward medical occurrence in a participant administered study drug and which does not necessarily have to have a causal relationship with the study drug. An AE is any sign, symptom, disease, or worsening of preexisting condition temporally associated with study therapy and irrespective of causality to study therapy. The number of participants who experienced an AE is presented.

Time frame: Up to approximately 88 months

Population: All randomized participants who received at least one dose of study treatment.

OS was defined as the time from the date of randomization to the date of death due to any cause. Participants without documented death at the time of analysis were censored at the date the participant was last known to be alive. The non-parametric Kaplan-Meier method was used to estimate the survival curve in each treatment group.

Time frame: Up to approximately 62 months

Population: All randomized participants based on the treatment group to which they were randomized.