Thalidomide dose selection for prevention of camrelizumab-induced reactive cutaneous capillary endothelial proliferation: a multicenter, randomized phase II trial

Reactive cutaneous capillary endothelial proliferation (RCCEP) is a characteristic cutaneous adverse event associated with immune checkpoint inhibitors. This study compared two prophylactic thalidomide doses to identify the more promising dose for further evaluation.

In this multicenter, randomized clinical trial, patients with advanced esophageal squamous cell carcinoma or non-small cell lung cancer (NSCLC) were randomly assigned to receive thalidomide 50 mg/day (Group A) or 100 mg/day (Group B) during first-line treatment with camrelizumab plus standard chemotherapy. The primary endpoint was overall RCCEP incidence; secondary endpoints included grade ≥3 RCCEP, median time to RCCEP onset, week 6 and week 9 RCCEP incidence, and safety.

A total of 72 patients were randomized. RCCEP occurred in 12 of 36 patients (33.3%) in Group A and 9 of 36 patients (25.0%) in Group B. RCCEP incidence at week 6 was 13.9% in Group A and 19.4% in Group B, and by week 9 was 25.0% and 19.4%, respectively. No grade ≥3 RCCEP occurred; all first RCCEP events were grade 1, with 1 grade 2 event reported in Group A. Among patients who developed RCCEP, median onset time was 1.49 and 1.31 months, respectively. Thalidomide-related adverse events occurred in 22.2% and 41.7% of patients, and grade 3 or higher thalidomide-related adverse events occurred in 8.3% and 22.2%, respectively. Serious adverse events occurred in 11.1% and 13.9% of patients, respectively.

Thalidomide 100 mg/day met the prespecified incidence-based dose-selection criterion compared with 50 mg/day but was associated with a higher incidence of grade 3 or higher toxicity. Further controlled evaluation is warranted.

https://clinicaltrials.gov/study/NCT06231680, identifier NCT06231680.