KEY TAKEAWAYS
- A phase 3 KEYNOTE-054 trial (NCT02362594) aimed to validate the durability of adjuvant pembrolizumab’s advantages observed in the prior primary analyses for resected high-risk stage III melanoma patients.
- Investigators randomly assigned 1019 patients to receive either pembrolizumab or placebo for 12 months.
- Pembrolizumab demonstrated a statistically significant improvement in recurrence-free and distant metastasis-free survival.
- Median follow-up of 4.9 years with data reported at 15, 36, and 42 months. The secondary endpoint was to evaluate the survival of patients.
- The 5-year analysis revealed that adjuvant pembrolizumab improves long-term survival in resected stage III melanoma.
In the prior primary analyses of the phase 3 trial, it was observed that administering adjuvant pembrolizumab for 12 months led to a significant increase in the duration of recurrence- and distant metastasis-free survival in patients diagnosed with resected high-risk stage III melanoma, as compared to placebo. To validate the durability of these advantages, extended-term data were required. A total of 1019 patients were randomly assigned to receive either 200 mg of pembrolizumab or placebo intravenously every 3 weeks for a total of 18 doses, which spans approximately 1 year. Investigators have previously reported data with a median follow-up of 15, 36, and 42 months. Researchers presented findings with a median follow-up duration of 4.9 years. They presented various outcomes, such as recurrence-free survival in the general population and the subset of patients with cancer who tested positive for programmed death ligand 1 (PD-L1). The study’s secondary endpoint was to evaluate the survival of patients without distant metastasis.
In the intention-to-treat population, pembrolizumab demonstrated a statistically significant improvement in recurrence-free survival compared to placebo (5-year recurrence-free survival rate of 55.4% [95% CI, 50.8 to 59.8] vs. 38.3% [95% CI, 33.9 to 42.7]; hazard ratio for recurrence or death, 0.61 [95% CI, 0.51 to 0.72]). Additionally, pembrolizumab showed a longer distant metastasis-free survival (5-year rate of distant metastasis-free survival, 60.6% [95% CI, 56.0 to 64.9] vs. 44.5% [95% CI, 39.9 to 48.9]; hazard ratio for distant metastasis or death, 0.62 [95% CI, 0.52 to 0.75]). Comparable observations were acquired in the subset of 853 individuals with tumors that exhibit positivity for PD-L1. The quinquennial evaluation of adjuvant therapy utilizing pembrolizumab yielded a persistent enhancement in the extended-term survival free from recurrence and distant metastasis compared to placebo among individuals with surgically removed stage III melanoma.
Source: https://evidence.nejm.org/doi/full/10.1056/EVIDoa2200214
Clinical Trail: https://clinicaltrials.gov/ct2/show/NCT02362594
Eggermont, A. M. M., Kicinski, M., Blank, C. U., Mandala, M., Long, G. V., Atkinson, V., Dalle, S., Haydon, A., Meshcheryakov, A., Khattak, A., Carlino, M. S., Sandhu, S., Larkin, J., Puig, S., Ascierto, P. A., Rutkowski, P., Schadendorf, D., Boers-Sonderen, M., Di Giacomo, A. M., & van den Eertwegh, A. J. M. (2022). Five-Year Analysis of Adjuvant Pembrolizumab or Placebo in Stage III Melanoma. NEJM Evidence. https://doi.org/10.1056/evidoa2200214
