Recurrence rates after anti-PD1 discontinuation for advanced melanoma: A systematic review and single-arm meta-analysis.

Abstract

e21536 Background: The introduction of immune checkpoint inhibitors, particularly anti-PD1 agents, has transformed the treatment landscape for unresectable stage III and stage IV melanoma. However, the optimal duration of therapy remains uncertain, and there is no consensus on the feasibility or timing of discontinuing anti-PD1 treatment. This systematic review and meta-analysis aimed to evaluate the outcomes associated with discontinuing anti-PD1 immunotherapy in patients with advanced melanoma. Methods: A systematic search of PubMed, Embase, and Cochrane databases was performed to identify studies assessing the cessation of anti-PD1 therapy in patients with unresectable stage III or stage IV melanoma, excluding those with disease progression (PD). Eligible studies included randomized controlled trials (RCTs) and observational studies, while overlapping populations were excluded. Heterogeneity was evaluated using the I² statistic, with values > 25% considered significant. Statistical analyses were conducted using OpenMeta [Analyst], and the study was registered on PROSPERO (CRD4202454378). Results: Seventeen studies (two post-hoc RCT analyses and 15 non-randomized cohort studies) comprising 1,769 patients were included. Of these, 1,492 patients (84.3%) received anti-PD1 monotherapy, while 277 patients (15.7%) received combination therapy with ipilimumab. Based on available data, BRAF mutations were reported in 460 of 1,466 patients (31.4%), and central nervous system metastases were observed in 200 of 1,472 patients (13.6%). The median follow-up duration ranged from 14.4 to 56 months, and the median treatment duration ranged from 4.7 to 36.5 months. Discontinuation was due to complete response (CR) in 569 patients (33.2%), immune-related adverse events (irAEs) in 589 patients (33.3%), and elective or other reasons in 611 patients (34.5%). The overall recurrence rate (RR) was 19.2% (95% CI, 15.1%–24.2%). Following therapy discontinuation, the 12-month progression-free survival (PFS) rate was 90.7% (95% CI, 84.0%–94.8%), and the 24-month PFS rate was 82.0% (95% CI, 73.1%–88.5%). Conclusions: This analysis highlights favorable PFS and RR following anti-PD1 therapy discontinuation, with superior outcomes observed in patients achieving CR and those who underwent combined therapy. Outcomes and subgroup analysis. Outcome Population Result (95% C.I.; I 2 ) 12-month PFS General 90.7% (95% CI, 84.0%–94.8%; I² = 89.5%) 24-month PFS General 82.0% (95% C.I.= 73.1%-88.5%; I² = 92.0%) CR 85.8% (95% C.I.= 79.5%-90.4%; I 2 = 76.52%) Combined therapy 78.2% (95% C.I.= 65.8%-90.6%; I 2 = 93.49%). RR General 19.2% (95% C.I.= 15.1%-24.2%; I² = 77.1%) CR 14% (95% C.I.= 10.5%-18.6%) IrAEs 25.5% (95% C.I.= 13.4%-37.6%) Monotherapy 22.3% (95% C.I.= 16.9%-27.7%; I 2 = 74.63%) Combined therapy 17.7% (95% C.I.= 7.4%-36.7%; I 2 = 83.98%)