Adjuvant immune checkpoint inhibition after complete resection

Updated results from KEYNOTE-054 and CheckMate-238 confirm previous observed benefits of adjuvant immune checkpoint inhibition with pembrolizumab and nivolumab, respectively.

In KEYNOTE-054, 1,019 patients with completely resected high-risk stage III melanoma were 1:1 randomised to adjuvant therapy with pembrolizumab (200 mg) or placebo every 3 weeks for a total of 18 doses (∼1 year) or until disease recurrence or unacceptable toxicity. The primary endpoint, recurrence-free survival (RFS), was in favour of pembrolizumab (HR 0.56 [1].

Updated results at 3.5 years of median follow-up showed that, compared with placebo, pembrolizumab significantly prolonged distant metastasis-free survival (DMFS) both in the overall population (65.3% vs 49.4%; HR 0.60; P<0.001) and in the PD-L1-positive tumour population (n=853; 66.7% vs 51.6%; HR 0.61; P<0.0001). Most benefit of adjuvant pembrolizumab was observed in patients with BRAF-mutated melanoma (64% vs 43%; HR 0.53) [2].

In CheckMate-238, 906 patients with completely resected high-risk, stage III/IV melanoma were 1:1 randomised to adjuvant therapy with nivolumab (3 mg/kg every 2 weeks) or ipilimumab (10 mg/kg every 3 weeks for 4 doses, every 12 weeks thereafter) for ≤1 year or until disease recurrence/unacceptable toxicity. At a minimum follow-up of 24 months, recurrence-free survival (RFS) was significantly longer for nivolumab versus ipilimumab (HR 0.66; P<0.0001) [3].

Now, at 48 months follow-up, median RFS was still in favour of nivolumab (52.4 vs 24.1 months; HR 0.71; P=0.003); RFS rate at 48 months was 52% and 41%, respectively [4]. DMFS also favoured nivolumab (median not reached vs 52.9 months; HR 0.79; P=0.045); DMSF rate at 48 months was 59% and 53%, respectively. However, at 48 months, overall survival rates were comparable (78% vs 77%, respectively; HR 0.87; P=0.3148).

1. Eggermont AMM, et al. J Clin Oncol 2020;Sep 18;JCO2002110.
2. Eggermont AMM, et al. Pembrolizumab versus placebo after complete resection of high-risk stage III melanoma: Final results regarding distant metastasis-free survival from the EORTC 1325-MG/Keynote 054 double-blinded phase III trial. ESMO 2020 Virtual Meeting, abstract LBA46.
3. Weber JS, et al. J Clin Oncol 36, 2018 (suppl; abstr 9502)
4. Weber JS, et al. Adjuvant nivolumab (NIVO) vs ipilimumab (IPI) in resected stage III/IV melanoma: 4-y recurrence-free and overall survival (OS) results from CheckMate 238. ESMO 2020 Virtual Meeting, abstract 1076O.

Posted on 25 November 20204 September 2023