(Melanoma) Is Pembrolizumab Effective? — Immune-Related Adverse Events and Recurrence-Free Survival
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Relationship Between Immune-Related Adverse Events and Recurrence-Free Survival in Stage III Melanoma
On January 2, 2020, Alexander Eggermont published in the medical journal JAMA Oncology a secondary analysis from the EORTC 1325/KEYNOTE-054 Phase 3 trial: "Association between immune-related adverse events and recurrence-free survival among patients with stage III melanoma treated with adjuvant pembrolizumab."
Trial Design
The EORTC 1325/KEYNOTE-054 Phase 3 trial enrolled 1,019 patients with resected stage IIIA/IIIB/IIIC melanoma, randomized 1:1 to:
- Pembrolizumab group: 200 mg on Day 1 of each 21-day cycle until disease progression or up to 1 year (N=509)
- Placebo group: Placebo on Day 1 of each 21-day cycle until disease progression or up to 1 year (N=502)
Primary endpoint: recurrence-free survival (RFS). Secondary endpoint: OS.
The initial analysis showed the pembrolizumab group had a 44% reduction in recurrence risk (HR 0.56) — a significant improvement. The secondary analysis was conducted based on the hypothesis that patients who develop immune-related adverse events (irAEs) during treatment with immune checkpoint inhibitors (anti-PD-1, anti-CTLA-4) may have better outcomes.
Baseline patient characteristics:
- BMI: Pembrolizumab group: <25 (30.3%), 25–29 (43.6%), ≥30 (23.8%); Placebo group: <25 (36.3%), 25–29 (38.6%), ≥30 (24.5%)
- Stage: IIIA: 15.1%, IIIB: ~46%, IIIC: ~39% (similar between groups)
- PD-L1 status: Positive ~83%, Negative ~11% (similar between groups)
Results
irAE incidence:
- At 3 months: Pembrolizumab 19.4% / Placebo 4.0%
- At 15 months: Pembrolizumab 37.4%
RFS results:
- Pembrolizumab group patients with irAEs vs. without irAEs: 39% reduction in recurrence risk (HR 0.61) — improvement observed
- Placebo group patients with irAEs vs. without irAEs: 37% increase in recurrence risk (HR 1.37)
Conclusions
Based on the EORTC 1325/KEYNOTE-054 secondary analysis, Alexander Eggermont concluded that in patients with stage III melanoma receiving adjuvant pembrolizumab, the occurrence of immune-related adverse events may be associated with improved recurrence-free survival.
Source: Association Between Immune-Related Adverse Events and Recurrence-Free Survival Among Patients With Stage III Melanoma Randomized to Receive Pembrolizumab or Placebo. JAMA Oncol. 2020 Jan 2.
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