Prevention of camrelizumab-induced RCCEP with thalidomide in advanced NSCLC treated with camrelizumab Plus chemotherapy as first-line treatment: a multicenter, double-blind, randomized phase II trial

Reactive cutaneous capillary endothelial proliferation (RCCEP) is a cutaneous adverse event associated with camrelizumab-based therapy and occurs at a high incidence. Although generally low grade, RCCEP may cause bleeding, irritation, and cosmetic discomfort, potentially affecting treatment adherence. Safe and effective preventive strategies remain limited. Thalidomide, an oral agent with anti-angiogenic and immunomodulatory properties, represents a potential alternative strategy for RCCEP prevention. This study evaluated the efficacy and safety of thalidomide for preventing camrelizumab-induced RCCEP in patients with advanced non–small cell lung cancer (NSCLC). In this randomized, placebo-controlled study, patients with advanced NSCLC receiving camrelizumab-based therapy were assigned to thalidomide or placebo group. The primary endpoint was RCCEP incidence of any grade. Secondary endpoints included time to first RCCEP onset (TTRO), time to first grade ≥ 3 RCCEP onset, incidence of grade ≥ 3 RCCEP, progression-free survival (PFS), overall survival (OS), objective response rate (ORR), disease control rate (DCR), duration of response (DoR), safety and outcomes of Quality of life (QoL). Between February 26, 2024, and December 26, 2024, 106 patients were enrolled and randomized to the thalidomide group ( N = 53) or the placebo group ( N = 53). RCCEP occurred in 17 patients (32.1%) in the thalidomide group and 34 patients (64.2%) in the placebo group, achieving the primary endpoint ( p = 0.0010). The median TTRO was markedly prolonged with thalidomide (55.7 weeks vs. 8.0 weeks; HR = 0.3; 95% CI, 0.2–0.6). No grade ≥ 3 RCCEP events occurred in either group; the incidence of grade 2 RCCEP was 9.4% and 11.3%, respectively. Regarding antitumor efficacy, median PFS was 9.2 versus 8.4 months (HR = 0.9, 95% CI 0.5–1.5; p = 0.6413) and ORR was 54.7% versus 50.9% (rate difference, 3.5% [95% CI, -15.5–22.5]). The safety profiles did not differ significantly, with comparable rates of treatment-emergent adverse events (TEAEs, 92.5% vs. 94.3%) and grade ≥ 3 TEAEs (22.6% vs. 26.4%). QoL remained stable over time and was comparable between groups. Thalidomide significantly reduced the incidence of camrelizumab-associated RCCEP, with no apparent differences in antitumor outcomes observed between the treatment groups. These findings support thalidomide as a potential prophylactic strategy for RCCEP in camrelizumab-based treatment. ClinicalTrials.gov identifier as NCT06276933.