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5-Year Follow-Up of KEYNOTE-006 Trial of Immunotherapy Regimens in Advanced Melanoma


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Caroline Robert, MD, PhD

Caroline Robert, MD, PhD

In a post hoc 5-year follow-up of the KEYNOTE-006 trial reported in The Lancet Oncology, Caroline Robert, MD, PhD, and colleagues found that pembrolizumab maintained overall and progression-free survival benefits over ipilimumab in patients with advanced melanoma. In the primary analysis from the trial, both pembrolizumab regimens had significantly prolonged overall and progression-free survival vs ipilimumab after a median follow-up of 22.9 months.

The open-label trial included 834 patients with advanced melanoma with known BRAF V600 status and up to one previous systemic therapy from 87 sites in 16 countries. They were randomly assigned 1:1:1 between September 2013 and March 2014 to receive either pembrolizumab at 10 mg/kg every 2 weeks (n = 279), pembrolizumab at 10 mg/kg every 3 weeks (n = 277), or four doses of ipilimumab at 3 mg/kg every 3 weeks (n = 278).

Pembrolizumab treatment continued for up to 24 months. Eligible patients who discontinued pembrolizumab with stable disease or better after receiving at least 24 months of treatment or discontinued with complete response after at least 6 months of treatment and then had disease progression could receive an additional 17 cycles of pembrolizumab. Data cutoff for this post hoc analysis was in December 2018.

The median follow-up in the current analysis was 57.7 months in surviving patients. Median time on treatment was 6.0 months for pembrolizumab (19% of patients completed 2 years of treatment; 13 patients received a second course) and 2.1 months for ipilimumab.

No significant differences were observed between the 2-week and 3-week pembrolizumab groups in median overall survival (31.1 vs 34.2 months, respectively) or median progression-free survival (8.4 vs 9.7 months). Thus, results for the two groups were combined for comparison with ipilimumab.

The median overall survival was 32.7 months in the combined pembrolizumab group vs 15.9 months in the ipilimumab group (hazard ratio [HR] = 0.73, = .00049); 5-year overall survival was 38.7% vs 31.0%. Median progression-free survival was 8.4 months vs 3.4 months (HR = 0.57, < .0001); 4-year progression-free survival was 23.0% vs 7.3%.

Among patients who were receiving first-line treatment in the trial, median overall survival was 38.7 months vs 17.1 months (HR = 0.73, = .0036) and median progression-free survival was 11.6 months vs 3.7 months (HR = 0.54, < .0001). Patients who were not receiving first-line treatment were those who previously received chemotherapy (14% and 10%), BRAF or MEK inhibitors (17% and 20%), or immunotherapy (3% and 4%). In patients receiving second-line treatment in the trial, median overall survival was 23.5 months vs 13.6 months (HR = 0.75, = .036).

In patients with BRAF V600 wild-type disease, median overall survival was 28.1 months vs 13.9 months (HR = 0.73, = .0048). In patients with BRAF V600E–mutant or BRAF V600K–mutant disease previously treated with a BRAF or MEK inhibitor, median overall survival was 20.4 months vs 11.9 months (HR = 0.71, = .054). In patients with BRAF V600E–mutant or BRAF V600K–mutant disease not previously treated with a BRAF or MEK inhibitor (patients with a normal baseline lactase dehydrogenase level), median overall survival was not reached vs 26.2 months (HR = 0.70, = .065).

The investigators concluded, “Pembrolizumab continued to show superiority over ipilimumab after almost 5 years of follow-up. These results provide further support for use of pembrolizumab in patients with advanced melanoma.” 

Robert C, et al: Lancet Oncol. July 22, 2019 (early release online).


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