Melanoma Institute Australia clinicians say their ‘practice changing’ study has shown that adjunct immunotherapy can reduce the spread of high risk melanoma after surgery.
Adjuvant pembrolizumab reduces the risk of disease recurrence or death in patients with stage IIB or IIC melanoma, according to the Australian investigators with the KEYNOTE-716 study.
First interim results from almost 1,000 patients across 16 countries in the RCT showed 11% of patients treated with 200 mg adjuvant pembrolizumab had disease recurrence compared to 17% of patients receiving placebo (HR 0.65; p=0.0066).
“The estimated 12-month recurrence-free survival rate was 90% (95% CI 87–93) in the pembrolizumab group and 83% (79–86) in the placebo group,” the authors reported in The Lancet.
This effect from pembrolizumab was sustained at the second interim analysis, when disease recurrence was 15% v 24% respectively in each patient group (HR 0.61).
“The estimated 18-month recurrence-free survival rate was 86% (95% CI 82–89) in the pembrolizumab group and 77% (95% CI 73–81) in the placebo group,” the authors added.
Recurrences were local, regional or locoregional (8%) versus distant (6%) in the pembrolizumab group compared to 10% and 12 % respectively in the placebo group.
The checkpoint inhibitor has previously been shown to significantly improve distant metastasis-free survival in patients with stage III melanoma compared to placebo (65·3% v 49·4%; HR 0·60 ; p<0·0001).
The latest data, previously presented at AACR and SMR meetings last year, led to the FDA approval of pembrolizumab as adjuvant treatment for adult and paediatric patients with high-risk stage II and stage III melanoma.
Study coauthor Professor Georgina Long, Co-Medical Director at Melanoma Institute Australia, told the limbic that the distant metastasis-free survival in stage II melanoma will be presented at the 2022 ASCO Annual Meeting in June.
“This is all about preventing that spread,” she said.
Professor Long said in all stages of melanoma, every sub-group of patients had benefitted.
“No matter what we look at in terms of their risk – in stage 4 with M1c disease or less aggressive M1a disease, in stage IIIA or stage IIIB – each sub group gets a benefit. Why wouldn’t you see that in stage II?”
“What did surprise us though was we got a positive result at the first interim analysis. We weren’t expecting that and that just speaks to how nasty stage IIB and C melanoma is. We thought we should have to wait a bit longer for events but in fact we see a lot of recurrences within that first 12 months and a lot of them are distant.”
The study showed that adverse events were common in both groups (93% v 89%) and consistent with the overall profile of immunotherapies in other adjuvant studies.
Grade 3–4 treatment-related events including rash, autoimmune hepatitis, colitis, and diarrhoea, occurred in 16% of patients in the pembrolizumab group and 4% of patients in the placebo group.
Treatment-related endocrine disorders such as hypothyroidism and hyperthyroidism occurred in 24% of patients in the pembrolizumab group and 3% of patients in the placebo group.
“These are really well tolerated drugs overall,” Professor Long said.
“Hypo and hyperthyroidism are common with this class of drugs. We see that across the board. Interestingly though, in the people who develop hypothyroidism…the common sequence of events is hyperthyroidism which then burns out.”
The quality of life and overall survival data is yet to be reported.
The study was funded by Merck Sharp & Dohme.