Patients with resected, high-risk, stage 3 melanoma who were randomized to receive Keytruda (pembrolizumab) achieved a three-year recurrence-free survival rate of 63.7% compared to 44.1% in patients randomized to placebo.
Following a median follow-up of three years, the use of immunotherapy agent Keytruda (pembrolizumab) for the adjuvant treatment of patients with resected, high-risk, stage 3 melanoma demonstrated a sustained and clinical meaningful improvement in recurrence-free survival (RFS), compared with placebo.
The Food and Drug Administration (FDA) approved Keytruda in this patient population in February 2019 after early results of the phase 3 EORTC 1325-MG/KEYNOTE-054 trial showed that the PD-1 inhibitor, compared to placebo, reduced the risk of recurrence or death by 43%.
Recently, the study authors published extended follow-up data in the Journal of Clinical Oncology. The aim of the updated analysis at a median follow-up of three years, according to the authors, was to analyze if the RFS benefit with Keytruda observed during the first follow-up was sustained. Additionally, the authors aimed to identify if certain patient characteristics — such as PD-L1 status, baseline stage of disease, and BRAF-V600 mutation status — were predictive of differences in treatment outcomes.
“Such analyses are important to confirm the initial findings with a shorter follow-up, and to compare them with those provided by the COMBI-AD trial in BRAF-V600–mutated melanoma at 44 months median follow-up,” they wrote.
From August 2015 to November 2016, 1,019 patients were randomly assigned to receive Keytruda (514 patients) or placebo (505 patients) across 123 cancer centers. Seventy-two patients who were assigned to receive Keytruda discontinued treatment as a result of a side effect, and 11 patients who received placebo had to discontinue from a side effect.
More patients in the placebo group (35.7%) discontinued therapy because of disease recurrence compared with those who received Keytruda (21.4%). More than half of both the Keytruda (58.3%) and placebo (59.8%) group completed one year of treatment.
Patients in the Keytruda arm achieved a three-year RFS rate of 63.7% compared with 44.1% in the placebo group. During the additional follow-up timeframe, there were more RFS events in patients who received the placebo (67 events) compared to those who received Keytruda (55 events). Moreover, 473 participants had either a recurrence or died — 37% in the Keytruda group and 56% in the placebo group.
Among 853 patients who were diagnosed with PD-L1-positive tumors, patients who received Keytruda experienced a three-year RFS rate of 65.3% compared to 46.4% in the placebo group.
Treatment with Keytruda also was effective in the 116 patients with PD-L1-negative tumors, with the three-year RFS rate being 56.9% in the study treatment group vs. 33.3% in the placebo group.
Patients with and without ulcerated melanomas experienced a benefit after receiving Keytruda. A patient’s age, sex and BMI at baseline did not significantly affect the treatment outcomes.
The incidence of side effects remained relatively unchanged from the previous analysis, the authors wrote, as only 25 patients were still receiving treatment during that time. Treatment-related side effects of any severity occurred in 78.8% of those who received Keytruda and 66.3% of those who received placebo.
Serious and severe side effects were more likely to occur in patients who received Keytruda (14.5%) than in placebo (3.4%).
“Current developments with neoadjuvant immunotherapy create new opportunities in a constantly changing landscape of (neo)adjuvant therapy in melanoma,” the authors wrote. “Adjuvant therapy in resected high-risk stage 3 melanoma provided at the three-year median follow-up a sustained and clinically meaningful improvement in RFS.”
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