First results on distant metastasis-free survival in stage II melanoma 

Results from the KEYNOTE-716 trial showed that patients with resected stage IIB or IIC melanoma had an improved distant metastasis-free survival (DMFS) if they were treated with adjuvant pembrolizumab instead of placebo. 

The risk of recurrence is substantial in patients with stage IIB or IIC melanoma [1]. The phase 3 KEYNOTE-716 trial (NCT03553836) randomised 976 patients with resected, high-risk, stage II melanoma 1:1 to pembrolizumab or placebo. Previous results from this trial showed that treatment with adjuvant pembrolizumab improved the recurrence-free survival (RFS) compared with placebo treatment (HR 0.65; P=0.0066) [2]. Prof. Georgina Long (The University of Sydney, Australia) presented the first findings of DMFS from the KEYNOTE-716 trial [3].

After a median follow-up of 27.4 months, the DMFS rate was improved in patients receiving pembrolizumab compared with patients receiving placebo (HR 0.64; P=0.0029; see Figure). Distant metastasis was detected in 12.9% and in 19.4% of the patients in the pembrolizumab arm and placebo arm, respectively. The median DMFS was not reached in either treatment groups. Moreover, the results were consistent across T-subcategories and other key subgroups. This interim analysis showed that RFS continued to favour the pembrolizumab arm over the placebo arm (HR 0.64).

Figure: Distant metastasis-free survival curves for pembrolizumab versus placebo [3]



NR, not reached; mo, month; Prembro, pembrolizumab.

No new safety issues emerged from the current analysis. In total, 17% and 5% of the patients experienced grade ≥3 adverse events (AEs) in the pembrolizumab and placebo group, respectively. In addition, 16% of the patients discontinued pembrolizumab due to AEs compared with 2% in the placebo group. Pruritus, rash, and diarrhoea were the most common grade ≥3 events in the experimental arm.

Dr Charlotte Ariyan (Memorial Sloan Kettering Cancer Center, NY, USA) argued that the risk of recurrence is approximately 40% in stage II patients and that the absolute risk reduction of these patients is 8% if they are treated with pembrolizumab. “Since the rate of grade ≥3 events is 17% and effective post-progression systemic therapies are available for these patients, the overall survival between patients who receive pembrolizumab or systemic therapies may be similar. We should improve the risk estimation of our patients by adding personalised risk calculators, genomic prediction models, and minimal residual disease values to the equation, to calculate which patients would benefit from what treatment.”

1. Egger ME, et al. Surgery. 2016;159(5):1412‒1421. 
2. Luke JJ, et al. Lancet. 2022;399:1718‒1729. 
3. Long GV, et al. Distantmetastasis-free survival withpembrolizumab versus placebo as adjuvanttherapy in stage IIB or IIC melanoma: The phase 3 KEYNOTE-716 study. LBA9500, ASCO 2022 Annual Meeting, 3–7 June, Chicago, IL, USA.

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Posted on 5 August 20225 August 2022