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Association details:
Biomarker:PD-L1 expression
Cancer:Melanoma
Drug:Keytruda (pembrolizumab) (PD1 inhibitor)
Direction:Sensitive
Evidence:
Evidence Level:
Sensitive: B - Late Trials
Source:
Title:

804P - Pembrolizumab versus placebo after complete resection of high-risk stage III melanoma: 5-year results of the EORTC 1325-MG/Keynote-054 double-blinded phase III trial

Published date:
09/05/2022
Excerpt:
We conducted the randomized phase 3 double-blind EORTC 1325/KEYNOTE-054 trial to evaluate pembrolizumab vs placebo in patients (pts) with resected high-risk stage III melanoma….1019 pts were randomized to pembrolizumab 200 mg (N=514) or placebo (N=505) every 3 weeks for a total of 18 doses or until disease recurrence or unacceptable toxicity....Pembrolizumab compared with placebo significantly prolonged RFS, DMFS and PRFS2 in the ITT population and in the PD-L1+ subgroup (N=853).
Evidence Level:
Sensitive: B - Late Trials
Source:
Title:

Adjuvant pembrolizumab versus placebo in resected stage III melanoma (EORTC 1325-MG/KEYNOTE-054): distant metastasis-free survival results from a double-blind, randomised, controlled, phase 3 trial

Published date:
04/12/2021
Excerpt:
In the 853 patients with PD-L1-positive tumours, 3·5-year distant metastasis-free survival was 66·7% (95% CI 61·8–71·2) in the pembrolizumab group and 51·6% (46·6–56·4) in the placebo group (HR 0·61 [95% CI 0·49–0·76]; p<0·0001)...Pembrolizumab adjuvant therapy provided a significant and clinically meaningful improvement in distant metastasis-free survival at a 3·5-year median follow-up, which was consistent with the improvement in recurrence-free survival.
DOI:
10.1016/S1470-2045(21)00065-6
Evidence Level:
Sensitive: B - Late Trials
Source:
Title:

LBA46 - Pembrolizumab versus placebo after complete resection of high-risk stage III melanoma: Final results regarding distant metastasis-free survival from the EORTC 1325-MG/Keynote 054 double-blinded phase III trial

Published date:
09/19/2020
Excerpt:
...At 3.5 yr median follow-up, pembrolizumab compared with placebo significantly prolonged DMFS in the overall population (3.5-yr DMFS rate: 65.3% vs 49.4%; HR 0.60, 95% CI 0.49-0.73; P<0.0001) and in the PD-L1-positive tumor (N=853; HR 0.61; 95% CI 0.49-0.76; P<0.0001)...The RFS improvement was confirmed (HR in the ITT population 0.59; 95% CI 0.49-0.70)....At 3.5-yr median follow-up, pembrolizumab adjuvant therapy provided a clinically meaningful improvement in DMFS in resected high-risk stage III melanoma pts.
Evidence Level:
Sensitive: B - Late Trials
Title:

Longer Follow-Up Confirms Recurrence-Free Survival Benefit of Adjuvant Pembrolizumab in High-Risk Stage III Melanoma: Updated Results From the EORTC 1325-MG/KEYNOTE-054 Trial

Published date:
09/18/2020
Excerpt:
In the 853 patients with PD-L1–positive tumors, the 3-year RFS rate was 65.3% (95% CI, 60.5% to 69.7%) in the pembrolizumab group and 46.4% (95% CI, 41.5% to 51.1%) in the placebo group (HR stratified by stage, 0.57; 99% CI, 0.43 to 0.74; P < .001; Fig 2B). Pembrolizumab was also consistently effective in the 116 patients with PD-L1–negative tumors, with the 3-year RFS rate being 56.9% (95% CI, 43.2% to 68.4%) in the pembrolizumab group and 33.3% (95% CI, 20.4% to 46.6%) in the placebo group. In resected high-risk stage III melanoma, pembrolizumab adjuvant therapy provided a sustained and clinically meaningful improvement in RFS at 3-year median follow-up. This improvement was consistent across subgroups.
DOI:
10.1200/JCO.20.02110 Journal of Clinical Oncology
Trial ID:
Evidence Level:
Sensitive: B - Late Trials
Source:
Title:

Pembrolizumab versus placebo after complete resection of high-risk stage III melanoma: New recurrence-free survival results from the EORTC 1325-MG/Keynote 054 double-blinded phase III trial at three-year median follow-up.

Published date:
05/13/2020
Excerpt:
At 3.05-yr median follow-up, pembrolizumab (190 RFS events) compared with placebo (283 RFS events) prolonged RFS, in the overall population and in the PD-L1 positive tumor subgroup (see Table). RFS was consistently prolonged across subgroups, in particular according to AJCC-7 staging, BRAF-V600 E/K mutation status.
DOI:
10.1200/JCO.2020.38.15_suppl.10000
Trial ID:
Evidence Level:
Sensitive: B - Late Trials
Title:

Adjuvant Pembrolizumab versus Placebo in Resected Stage III Melanoma

Published date:
05/10/2018
Excerpt:
At a median follow-up of 15 months, pembrolizumab was associated with significantly longer recurrence-free survival than placebo in the overall intention-to-treat population (1-year rate of recurrence-free survival, 75.4% [95% confidence interval {CI}, 71.3 to 78.9] vs. 61.0% [95% CI, 56.5 to 65.1]; hazard ratio for recurrence or death, 0.57; 98.4% CI, 0.43 to 0.74; P<0.001) and in the subgroup of 853 patients with PD-L1-positive tumors (1-year rate of recurrence-free survival...
DOI:
10.1056/NEJMoa1802357
Evidence Level:
Sensitive: C1 - Off-label
  (Approved for Non Small Cell Lung Cancer)
New
Excerpt:
Keytruda as monotherapy is indicated for the first line treatment of metastatic non small cell lung carcinoma in adults whose tumours express PD L1 with a ≥ 50% tumour proportion score (TPS) with no EGFR or ALK positive tumour mutations.
Evidence Level:
Sensitive: C2 – Inclusion Criteria
New
Go to data
Title:

Adjuvant immunotherapy with anti-PD-1 monoclonal antibody Pembrolizumab (MK-3475) versus placebo after complete resection of high-risk Stage III melanoma: A randomized, double-blind Phase 3 trial of the EORTC Melanoma Group.

Excerpt:
...Mandatory to ship tumor sample for evaluation of PD-L1 expression.
Evidence Level:
Sensitive: C3 – Early Trials
Title:

PD-L1 Expression on Circulating Tumor Cells May Be Predictive of Response to Pembrolizumab in Advanced Melanoma: Results from a Pilot Study

Published date:
12/05/2019
Excerpt:
PD‐L1 expression on CTCs may be predictive of response to pembrolizumab and longer PFS.
DOI:
https://doi.org/10.1634/theoncologist.2019-0557
Evidence Level:
Sensitive: C3 – Early Trials
Source:
Title:

Loss of HLA class I expression and T-cell infiltration or PD-L1 expression are associated with different response patterns to pembrolizumab in melanoma

Published date:
10/01/2018
Excerpt:
We have retrospectively analyzed 18 patients treated by pembrolizumab for metastatic melanoma...We found that only PD-L1 expression and the presence of T-cell infiltration were associated with a better response to pembrolizumab: PD-L1 expression (p = 0,043), T-cell infiltration (p = 0,025) and T-cell location at the periphery of the tumoral nodules (p = 0,025). PD-L1 expression and the presence of T lymphocytes were also associated with a longer survival.
DOI:
https://doi.org/10.1093/annonc/mdy289.017