KEYTRUDA is indicated for the adjuvant treatment of patients with melanoma with involvement of lymph node(s) following complete resection.
From The New England Journal of Medicine, Eggermont AMM, Blank CU, et al. Adjuvant pembrolizumab versus placebo in resected stage III melanoma. N Engl J Med. 2018;378(19):1789–1801. Copyright © Massachusetts Medical Society. Reprinted with permission from Massachusetts Medical Society.
- According to Kaplan-Meier estimates, the probability of a patient treated with KEYTRUDA being alive and recurrence free was 75.4% at 12 months and 71.4% at 18 months.1
- KEYTRUDA significantly reduced the risk of disease recurrence or death (43% reduction) compared with placebo (HRa=0.57 [95% CI, 0.46–0.70]; P<0.001).
- Median RFS was not reached with KEYTRUDA (vs 20.4 months with placebo) by the time interim analysis was conducted (1.25 years).1
- In this study, the number needed to treat (NNT) with KEYTRUDA, as compared to observation, to prevent one recurrence was approximately 6 patients at 18 months.1
aBased on the stratified Cox proportional hazard model. Stratified by American Joint Committee on Cancer (AJCC), 7th ed. stage.
bP value is compared with 0.008 of the allocated alpha for this interim analysis.
Placebo = complete surgical resection followed by observation.
- For the co-primary end point of RFS in patients whose tumors were considered PD‑L1 positive, KEYTRUDA demonstrated significantly prolonged RFS compared with placebo (HR=0.54, 95% CI, 0.42–0.69; P<0.001).
- The RFS benefit for KEYTRUDA compared with placebo was observed regardless of tumor PD-L1 expression.
BRAF = B-Raf proto-oncogene, serine/threonine kinase; PD-L1 = programmed death ligand 1; HR = hazard ratio; CI = confidence interval.
KN-054 was not powered to detect differences in the treatment effect in these subgroups; therefore, results from exploratory analyses should be interpreted with caution because of the modest patient numbers and potential imbalances in baseline characteristics within the subgroups.2
cThe green diamond is centered on the overall hazard ratio (dashed line) and covers its 98.4% confidence interval. In the subgroup analyses, 99% confidence intervals (green lines) are presented.2
dTumor PD-L1 expression was assessed by immunohistochemistry and a ≥1% expression in stained cells was used to define the positive population.2
eAJCC denotes American Joint Committee on Cancer, 7th ed. classification.2
NCCN Guidelines® recommend pembrolizumab (KEYTRUDA) as an option for adjuvant treatment of select patients with resected stage III cutaneous melanoma regardless of BRAF mutation status (category 1).3,f
Category 1 = based upon high-level evidence, there is uniform National Comprehensive Cancer Network® (NCCN®) consensus that the intervention is appropriate.3
fPembrolizumab is a category 1 option for patients with AJCC 7th edition stage IIIA with SLN metastasis > 1mm or stage IIIB/C confined to the lymph nodes.
NCCN makes no warranties of any kind whatsoever regarding their content, use, or application and disclaims any responsibility for their application or use in any way.
AJCC = American Joint Committee on Cancer; SLN = sentinel lymph node.
The KEYNOTE-054 clinical study, conducted in collaboration with the European Organisation for Research and Treatment of Cancer (EORTC), included treatment with KEYTRUDA compared with observation following complete surgical resection of high-risk melanoma (the placebo arm), as well as anti–PD-1 rechallenge (crossover design).1
- The primary end point was investigator-assessed RFS in the whole population and in the population with PD-L1–positive tumors where RFS was defined as the time between the date of randomization and the date of first recurrence (local, regional, or distant metastasis) or death, whichever occurs first.
- KEYTRUDA was studied across a broad spectrum of nonmetastatic melanoma patients with nodal involvement regardless of PD-L1 expression or BRAF status.1
PD-1 = programmed death receptor-1; IV = intravenous; Q3W = every 3 weeks.
gIncluded patients with AJCC (2002) stage III melanoma.