The Phase 3 KEYNOTE-937 study (NCT03867084) investigating pembrolizumab as adjuvant therapy for hepatocellular carcinoma completed its primary data collection on March 20, 2025. This trial evaluated the safety and efficacy of pembrolizumab versus placebo in participants who achieved a complete radiological response after surgical resection or local ablation. While primary efficacy endpoints are pending, initial data on adverse events and quality of life measures have been reported.
Background
The KEYNOTE-937 study investigated pembrolizumab (also known as Keytruda) as an adjuvant therapy. The trial focused on participants with hepatocellular carcinoma (HCC) who had achieved a complete radiological response following surgical resection or local ablation.
Trial design
The KEYNOTE-937 study (NCT03867084) was a Phase 3, randomized, placebo-controlled trial that enrolled 959 participants. The study investigated pembrolizumab versus placebo as adjuvant therapy in participants with hepatocellular carcinoma (HCC) who had achieved a complete radiological response after surgical resection or local ablation. The primary hypotheses of the study were that adjuvant pembrolizumab would be superior to placebo with respect to recurrence-free survival (RFS) as assessed by blinded independent central review (BICR) and overall survival (OS).
Key results
Data from the trial included information on adverse events and quality of life measures:
- For the outcome "Number of Participants Who Experienced an Adverse Event (AE)", 430 participants in the pembrolizumab group experienced an AE, compared to 397 participants in the placebo group.
- Regarding discontinuation due to an AE, 58 participants in the pembrolizumab group discontinued study treatment, while 17 participants in the placebo group discontinued.
Quality of Life (QoL) was assessed using the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) and the QLQ-Hepatocellular Carcinoma Module (QLQ-HCC18). Several QoL outcomes were analyzed for changes from baseline, including Global Health Status, Physical Functioning, Role Functioning, and Abdominal Swelling scales. For these analyses, no statistically significant differences were observed between the pembrolizumab and placebo groups.
- For the EORTC QLQ-C30 Combined Global Health Status (GHS) / Quality of Life (QoL) Scale Score, the mean difference (final values) was -1.36 (95.0% CI: -3.7 to 0.99) with a p-value of 0.2563.
- For the EORTC QLQ-C30 Physical Functioning Scale Score, the mean difference was -0.24 (95.0% CI: -2.28 to 1.8) with a p-value of 0.8165.
- For the EORTC QLQ-HCC18 Abdominal Swelling Scale Score, the mean difference was 1.34 (95.0% CI: -1.24 to 3.92) with a p-value of 0.3091.
Other QoL analyses, including for Role Functioning, also reported p-values greater than 0.05, indicating no statistically significant differences between treatment arms for these specific measures.
What this means
The completion of primary data collection for the KEYNOTE-937 trial marks a significant step in evaluating pembrolizumab as an adjuvant therapy for resected or ablated hepatocellular carcinoma. While the primary efficacy endpoints of recurrence-free survival and overall survival are yet to be reported, the available quality of life data did not show statistically significant differences between the pembrolizumab and placebo groups across the measured scales. The data also indicates a higher incidence of adverse events and discontinuations due to adverse events in the pembrolizumab arm compared to placebo. Further analysis of the primary efficacy endpoints will be crucial to determine the overall benefit-risk profile of pembrolizumab in this adjuvant setting.
Source
The information regarding the primary completion of this trial was obtained from ClinicalTrials.gov, a public database of clinical studies. The update for study NCT03867084, titled "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)," was posted on 2025-03-20 on clinicaltrials.gov.