Trial Outcomes & Findings for Safety and Efficacy of Pembrolizumab (MK-3475) Versus Placebo as Adjuvant Therapy in Participants With Hepatocellular Carcinoma (HCC) and Complete Radiological Response After Surgical Resection or Local Ablation (MK-3475-937 / KEYNOTE-937) (NCT NCT03867084)

Participants at least 18 years of age with hepatocellular carcinoma (HCC) and who had complete radiological response after surgical resection or local ablation were recruited.

Of 1313 participants screened, 959 participants were randomized 1:1 to receive either pembrolizumab or placebo.

Safety and Efficacy of Pembrolizumab (MK-3475) Versus Placebo as Adjuvant Therapy in Participants With Hepatocellular Carcinoma (HCC) and Complete Radiological Response After Surgical Resection or Local Ablation (MK-3475-937 / KEYNOTE-937)

RFS was defined as the time from randomization to first documentation of disease recurrence (local, regional, or distant) as assessed by blinded independent central review (BICR) or by pathology consistent with HCC if required per the site's standard of care, or death due to any cause (both cancer and non-cancer causes of death), whichever occurred first. RFS was reported for each arm.

OS was defined as the time from randomization to death due to any cause. OS was reported for each arm.

An AE was defined as any unfavorable and unintended sign, symptom, or disease (new or worsening) temporally associated with the use of study therapy, regardless of whether or not a causal relationship with the study therapy was determined. The number of participants who experienced an AE were reported.

An AE was defined as any unfavorable and unintended sign, symptom, or disease (new or worsening) temporally associated with the use of study therapy, regardless of whether or not a causal relationship with the study therapy was determined. The number of participants who discontinued study treatment due to an AE were reported.

The EORTC QLQ-C30 is a cancer specific health-related quality-of life (QoL) questionnaire. Participants responded to the questions regarding Global Health Status (GHS; "How would you rate your overall health during the past week?") and Quality of Life ("How would you rate your overall quality of life during the past week?") are scored on a 7-point scale (1= Very poor to 7=Excellent). The combined score of GHS (Item 29) and QoL (Item 30) was computed by averaging the raw scores of the 2 items and then applying a linear transformation to standardize the average score, so that the combined scores range from 0-100. A higher score indicated a better outcome. The change from baseline in GHS (EORTC QLQ-C30 Item 29) and QoL (EORTC QLQ-C30 Item 30) combined score was reported.

The EORTC QLQ-C30 is a cancer specific health-related quality of life questionnaire. Participants responded to 5 questions about their physical functioning (Items 1-5) are scored on a 4-point scale (1=Not at All to 4=Very Much). The combined score of items 1 to 5 was computed by averaging the raw scores of the 5 items and then applying a linear transformation to standardize the average score, so that the combined scores range from 0-100. Higher scores indicated better physical functioning. The change from baseline in EORTC QLQ-C30 Physical Functioning (Items 1-5) combined score was reported.

The EORTC QLQ-C30 is a cancer specific health-related quality of life questionnaire. The role functioning score was based on participant responses to questions scored on a 4-point scale (1=Not at All to 4=Very Much). The combined score was computed by averaging the raw scores of Items 6 and 7 and then applying a linear transformation to standardize the average score, so that the combined scores range from 0-100. Higher scores indicated better role functioning. The change from baseline in EORTC QLQ-C30 Role Functioning (Items 6 and 7) combined score was reported.

The EORTC QLQ-HCC18 is an HCC-specific questionnaire, administered in addition to the EORTC QLQ-C30. The abdominal swelling scale score was based on participant responses to questions 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 0-100. Higher scores indicated more severe symptoms/problems. Change from baseline in the EORTC QLQ-HCC18 abdominal swelling scale score was reported.

The EORTC QLQ-HCC18 is an HCC-specific questionnaire, administered in addition to the EORTC QLQ-C30. The fatigue scale score was based on participant responses to questions scored on a 4-point scale (1=Not at All to 4=Very Much). The combined score was computed by averaging the raw scores of the items and then applying a linear transformation to standardize the average score, so that the combined scores range from 0-100. Higher scores indicated more severe symptoms/problems. Change from baseline in the EORTC QLQ-HCC18 fatigue scale score was reported.

The EORTC QLQ-HCC18 is an HCC-specific questionnaire, administered in addition to the EORTC QLQ-C30. The pain scale score was based on participant responses to questions scored on a 4-point scale (1=Not at All to 4=Very Much). The combined score was computed by averaging the raw scores of the items and then applying a linear transformation to standardize the average score, so that the combined scores range from 0-100. Higher scores indicated more severe symptoms/problems. Change from baseline in the EORTC QLQ-HCC18 pain scale score was reported.

The EQ-5D-5L is a standardized instrument for use as a measure of health outcome. The VAS is a component of the EQ-5D-5L that asked participants to rate their overall health on a vertical visual analogue scale, with the scale's ends labelled 'The best health you can imagine' (equivalent to a score of 0) and 'The worst health you can imagine' (equivalent to a score of 100).

EORTC QLQ-C30 is a questionnaire to assess QoL of cancer patients. Participants responded to questions on GHS ("How would you rate your overall health during the past week?") and QoL ("How would you rate your overall QoL during the past week?") were scored on a 7-point scale (1= Very poor to 7=Excellent). The combined score of GHS (Item 29) and QoL (Item 30) was computed by averaging raw scores of the 2 items and applying a linear transformation to standardize the average score, so that the combined scores range from 0-100. A higher score indicated a better outcome. TTD was defined as the time from baseline to first onset of ≥10-point negative change (decrease) from baseline in GHS-QoL combined score. A longer TTD indicated a better outcome.

EORTC QLQ-C30 is a questionnaire to assess the overall QoL of cancer patients. Participants responded to 5 questions about their physical functioning (Items 1 to 5) are scored on a 4-point scale (1=Not at All to 4=Very Much). The combined score of items 1 to 5 was computed by averaging the raw scores of the 5 items and then applying a linear transformation to standardize the average score, so that the combined scores range from 0-100. A higher score indicated a better outcome. TTD was defined as the time from baseline to first onset of ≥10-point negative change (decrease) from baseline in physical functioning (Items 1 to 5). A longer TTD indicated a better outcome.

EORTC QLQ-C30 is a questionnaire to assess the overall QoL of cancer patients. Participants responded to questions about their role functioning (Items 6 and 7) are scored on a 4-point scale (1=Not at All to 4=Very Much). The combined score of Items 6 and 7 was computed by averaging the raw scores of the items and then applying a linear transformation to standardize the average score, so that the combined scores range from 0-100. A higher score indicated a better outcome. TTD was defined as the time from baseline to first onset of ≥10-point negative change (decrease) from baseline in physical functioning (Items 6 and 7). A longer TTD indicated a better outcome.

The EORTC QLQ-HCC18 is an HCC-specific questionnaire, administered in addition to the EORTC QLQ-C30. The abdominal swelling scale score was based on participant responses to questions 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 0-100. Higher scores indicated more severe symptoms/problems. The TTD in EORTC QLQ-HCC18 abdominal swelling scale score was reported, defined as the time to first onset of a ≥10 point decrease from baseline.

The EORTC QLQ-HCC18 is an HCC-specific questionnaire, administered in addition to the EORTC QLQ-C30. The fatigue scale score was based on participant responses to questions scored on a 4-point scale (1=Not at All to 4=Very Much). The combined score was computed by averaging the raw scores of the items and then applying a linear transformation to standardize the average score, so that the combined scores range from 0-100. Higher scores indicated more severe symptoms/problems. The TTD in EORTC QLQ-HCC18 fatigue scale score was reported, defined as the time to first onset of a ≥10 point decrease from baseline.

The EORTC QLQ-HCC18 is an HCC-specific questionnaire, administered in addition to the EORTC QLQ-C30. The pain scale score was based on participant responses to questions scored on a 4-point scale (1=Not at All to 4=Very Much). The combined score was computed by averaging the raw scores of the items and then applying a linear transformation to standardize the average score, so that the combined scores range from 0-100. Higher scores indicated more severe symptoms/problems. The TTD in EORTC QLQ-HCC18 pain scale score was reported, defined as the time to first onset of a ≥10 point decrease from baseline.