- In patients with melanoma:
- Stage IIB / IIC disease is associated with a high risk of relapse
- 5-year melanoma-specific survival outcomes are similar to those for patients with stage IIIB disease:
- Highlighting a need for additional treatment strategies for these patients
- The randomized, phase 3 KEYNOTE-716 trial:
- Was undertaken to evaluate the efficacy and safety of adjuvant pembrolizumab in patients with:
- Newly diagnosed resected stage IIB / IIC melanoma with a negative sentinel lymph node biopsy
- Was undertaken to evaluate the efficacy and safety of adjuvant pembrolizumab in patients with:
- A total of 967 patients were randomly assigned to pembrolizumab or placebo:
- Administered every 3 weeks for up to 17 cycles
- In previous analyses, pembrolizumab demonstrated significant efficacy improvements in RFS and DMFS over placebo
- In the last update, after a median follow-up of 27.4 months, median DMFS was not reached in either arm (HR 0.64, 95% CI [0.47, 0.88]; P = .0029)
- In the current update:
- After a median follow-up of 39.4 months, median DMFS was still not reached in either arm, and there was a consistent benefit with pembrolizumab (HR 0.59, 95% CI [0.44, 0.79];)
- The RFS benefit with pembrolizumab was also maintained in the current follow-up:
- The 3-year RFS rates were 76.2% with pembrolizumab and 63.4% with placebo, and median RFS was not reached in either arm (HR 0.62, 95% CI [0.49, 0.79])
- The DMFS and RFS benefit with pembrolizumab was observed in both stage IIB / IIC melanoma:
- An earlier analysis suggested that there may be a lesser benefit with pembrolizumab in patients with stage IIC disease:
- This was no longer observed with additional follow-up
- We now see that this discrepancy has been resolved with longer follow-up:
- The overall impact of pembrolizumab as adjuvant therapy appears to be similar across stages
- An earlier analysis suggested that there may be a lesser benefit with pembrolizumab in patients with stage IIC disease:
- Safety outcomes were similar to those reported in the previous analyses
- Grade 3/4 treatment-related adverse events (AEs) occurred in 17.2% of patients receiving pembrolizumab and 5.1% of those receiving placebo; grade 3/4 immune-related AEs and infusion reactions occurred in 11.0% and 1.2% of patients, respectively.
- Treatment-related AEs led to discontinuation in 15.9% of patients receiving pembrolizumab and 2.5% receiving placebo
- Investigators noted that the overall survival analyses are forthcoming
- Next Steps
- Looking ahead, one related area of discussion revolves around the role of sentinel lymph node biopsy for patients with melanoma:
- If the patient has a deep primary melanoma, adjuvant pembrolizumab should be discussed with the patient whether the nodes are involved or not:
- However, this remains an area of debate
- If the patient has a deep primary melanoma, adjuvant pembrolizumab should be discussed with the patient whether the nodes are involved or not:
- Looking ahead, one related area of discussion revolves around the role of sentinel lymph node biopsy for patients with melanoma:
- Patient selection beyond the current AJCC classification will be key for the future:
- To identify patients with a particularly favorable prognosis for whom treatment could be spared and to identify those patients with a poor prognosis who would benefit from additional therapy:
- Biomarker studies are underway to guide us in this important next step
- To identify patients with a particularly favorable prognosis for whom treatment could be spared and to identify those patients with a poor prognosis who would benefit from additional therapy:
- Another area of ongoing research is the potential use of combination immunotherapy regimens in the adjuvant setting:
- Among the ongoing trials are:
- KEYVIBE-010:
- Evaluating pembrolizumab plus the anti-TIGIT antibody vibostolimab in patients with high-risk resected stage IIB, IIC, III, and IV melanoma
- KEYNOTE-942:
- Evaluating pembrolizumab plus a personalized neoantigen therapy (V940) for high-risk melanoma
- KEYVIBE-010:
- Among the ongoing trials are:
- References
- Luke JJ, Rutkowski P, Queirolo P, et al. Pembrolizumab versus placebo as adjuvant therapy in completely resected stage IIB or IIC melanoma (KEYNOTE-716): a randomised, double-blind, phase 3 trial. Lancet. 2022;399(10336):1718-1729.
- Long GV, Luke JJ, Khattak MA, et al. Pembrolizumab versus placebo as adjuvant therapy in resected stage IIB or IIC melanoma (KEYNOTE-716): distant metastasis-free survival results of a multicentre, double-blind, randomised, phase 3 trial. Lancet Oncol. 2022;23(11):1378-1388.
- Gershenwald JE, Scolyer RA, Hess KR, et al. Melanoma staging: evidence-based changes in the American Joint Committee on Cancer eighth edition cancer staging manual. CA Cancer J Clin. 2017;67(6):472-492.
- Egger ME, Bhutiani N, Farmer RW, et al. Prognostic factors in melanoma patients with tumor-negative sentinel lymph nodes. Surgery. 2016;159(5):1412-1421.
Rodrigo Arrangoiz MS, MD, FACS, FSSO 