Adjuvant immunotherapy reduces risk of disease recurrence in stage II melanoma

The first interim analysis of KEYNOTE-716 suggests adjuvant pembrolizumab to be superior to standard-of-care observation for adult and children with completely resected high-risk melanoma.

Patients with stage IIB-C melanoma are at high risk of disease recurrence and survival outcomes are similar to stage IIIA-B melanoma [1]. In patients with stage III melanoma, adjuvant therapy with pembrolizumab prolonged recurrence-free survival (RFS) as well as distant metastasis-free survival (DMFS) [2]. The phase 3, double-blind KEYNOTE-716 trial (NCT03553836) evaluated pembrolizumab versus placebo in patients with resected stage IIB or IIC melanoma. Dr Jason Luke (UPMC Hillman Cancer Center, PA, USA) presented results from the first interim analysis of KEYNOTE-716 [3].

A total of 976 patients (64% stage IIB, 34.8% stage IIC; aged ≥12 years with complete resection of cutaneous melanoma and with negative sentinel lymph node biopsy) were enrolled and randomised 1:1 to pembrolizumab (200 mg; 2 mg/kg for paediatric patients) or placebo every 3 weeks for 17 cycles (up to 1 year). Treatment continued until disease recurrence or unacceptable toxicity. The primary endpoint was RFS per investigator assessment. Secondary endpoints were DMFS, overall survival (OS), safety, and quality of life.

At median follow-up of 14.4 months, pembrolizumab significantly prolonged RFS versus placebo (HR 0.65; P=0.00658; median not reached for both). The 12-month RFS rate was 90.5% versus 83.1%. At data cut-off, 11.1% of patients treated with pembrolizumab had a recurrence versus 16.8% of patients treated with placebo. Pembrolizumab almost halved the distant recurrence rate (4.7% vs 7.8%).

The incidence of grade ≥3 adverse events (AEs) was higher with pembrolizumab than with placebo, both for any-cause AEs (25.9% vs 17.1%) and for drug-related AEs (16.1% vs 4.3%). Altogether, 15.3% of patients discontinued pembrolizumab due to a drug-related AE, compared with 2.5% receiving placebo. Immune-mediated AEs occurred in 36.2% versus 8.4%, most commonly hypothyroidism (15.7% vs 3.5%) and hyperthyroidism (10.4% vs 0.6%). Most were grade 1–2 in severity. Quality of life was maintained with both adjuvant pembrolizumab and placebo.

“Adjuvant pembrolizumab is an effective treatment option with a favourable benefit risk profile for patients with high-risk stage II melanoma,” concluded Dr Luke.

1. Luke JJ, et al. Nat Rev Clin Oncol. 2017;14:463–482.
2. Eggermont AMM, et al. Lancet Oncol. 2021;22:643–645.
3. Luke JJ, et al. Pembrolizumab versus placebo after complete resection of high-risk stage II melanoma: Efficacy and safety results from the KEYNOTE-716 double-blind phase III trial. Abstract LBA3_PR, ESMO Congress 2021, 16–21 September.

 

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Posted on 19 November, 202115 February, 2024