The Phase 3 trial for pembrolizumab (Keytruda) in patients with Stage III-IV high-risk melanoma that has been surgically removed reached its primary completion on September 15, 2023. The trial data indicated that pembrolizumab led to an overall survival of 82% compared to 76% for standard of care, and a relapse-free survival of 58% versus 49% for standard of care.
Background
Pembrolizumab (Keytruda) is an immunotherapy drug that was investigated in this study for patients with Stage III-IV high-risk melanoma that had been surgically removed. The trial compared pembrolizumab against a standard of care regimen, which was physician/patient choice of either high-dose recombinant interferon alfa-2B or ipilimumab. Immunotherapy with monoclonal antibodies like pembrolizumab is designed to help the body's immune system attack cancer cells.
Trial design
The randomized Phase 3 study (NCT02506153) enrolled 1301 participants diagnosed with Clinical Stage III Cutaneous Melanoma AJCC v8, Clinical Stage IV Cutaneous Melanoma AJCC v8, Metastatic Cutaneous Melanoma, Metastatic Mucosal Melanoma, or Metastatic Non-Cutaneous Melanoma that had been removed by surgery. The trial compared pembrolizumab against a standard of care arm, which consisted of physician/patient choice of either high-dose recombinant interferon alfa-2B or ipilimumab.
Key results
The trial's key measurements showed the following outcomes:
- Overall Survival (OS): Pembrolizumab achieved an OS of 82% of participants, compared to 76% of participants for the FDA Approved Regimen (Standard of Care).
- Relapse-free Survival (RFS): Pembrolizumab achieved an RFS of 58% of participants, compared to 49% of participants for the FDA Approved Regimen (Standard of Care).
- Overall Survival (OS) in PD-L1 Positive Participants: Pembrolizumab achieved an OS of 83% of participants, compared to 79% of participants for the FDA Approved Regimen (Standard of Care).
- Relapse-free Survival (RFS) in PD-L1 Positive Participants: Pembrolizumab achieved an RFS of 60% of participants, compared to 51% of participants for the FDA Approved Regimen (Standard of Care).
Regarding Grade 3 through 5 adverse events related to study drugs, the trial reported:
- For one measurement, 2 participants in the pembrolizumab arm experienced these events, compared to 6 participants in the FDA Approved Regimen arm.
- For another measurement, 2 participants in the pembrolizumab arm experienced these events, compared to 1 participant in the FDA Approved Regimen arm.
What this means
The results from this Phase 3 trial suggest that pembrolizumab may offer an improved treatment option for patients with Stage III-IV high-risk melanoma that has been surgically removed. The observed improvements in both overall survival and relapse-free survival, including in the PD-L1 positive subgroup, indicate a potential benefit over the current standard of care. The adverse event data shows mixed results, with pembrolizumab demonstrating fewer Grade 3-5 adverse events in one comparison, but slightly more in another. These findings will be important for clinicians considering adjuvant therapy options for this patient population.
Source
The information for this drug update was sourced from ClinicalTrials.gov, a public database of clinical studies. The primary completion date for study NCT02506153, titled "Physician/Patient Choice of Either High-Dose Recombinant Interferon Alfa-2B or Ipilimumab, Versus Pembrolizumab in Treating Patients With Stage III-IV High Risk Melanoma That Has Been Removed by Surgery", was recorded as September 15, 2023 on clinicaltrials.gov.