Efficacy of Thymosin α1 in Management of Radiation Pneumonitis in Patients With Locally Advanced Non-Small Cell Lung Cancer Treated With Concurrent Chemoradiotherapy: A Phase 2 Clinical Trial (GASTO-1043)

Purpose: To evaluate the efficacy of thymosin alpha 1 in management of radiation pneumonitis (RP) in patients with locally advanced non-small cell lung cancer (LANSCLC) treated with concurrent chemoradiotherapy (CCRT). Methods and Materials: This phase 2, single-arm trial enrolled patients with unresectable LANSCLC of 18 to 75 years' old and an Eastern Cooperative Oncology Group performance status of 0 to 1. Eligible patients received definitive CCRT and weekly thymosin alpha 1 from the start of CCRT until 2 months after CCRT. Patients were administered 51 Gy in 17 daily fractions or 40 Gy in 10 daily fractions in the first course followed by a re-evaluation and those patients without disease progression had an adaptive plan of 15 Gy in 5 daily fractions or 24 Gy in 6 daily fractions as a boost. Concurrent chemotherapy consisted of weekly docetaxel (25 mg/m(2)) and nedaplatin (25 mg/m(2)) during radiation therapy. The primary endpoint was the incidence of Grade (G) >= 2 RP. Secondary endpoints included the incidence of late pulmonary fibrosis, total lymphocyte count (TLC), serum C-reactive protein (CRP) levels, and the composition of gut microbiota. TLC and CRP data were collected at baseline, 2 to 3 weeks during CCRT, the end of CCRT, 2 and 6 months after CCRT. Fecal samples were collected at baseline and the end of CCRT. Patients treated with CCRT but without thymosin alpha 1 intervention during the same period were selected as the control group by the propensity score matching method. Results: Sixty-nine patients were enrolled in the study, and another 69 patients were selected as the control group. The incidence of G >= 2 RP was lower in the study group compared with control cases (36.2% vs 53.6%, P = .040). G1 late pulmonary fibrosis occurred in 2 (3.7%) patients of the control group compared with no event in the study group (P = .243). Compared with the control group, the incidence of G3 to G4 lymphopenia (19.1% vs 62.1%, P < .001) was lower, and the median TLC nadir (0.51 k/mu L vs 0.30 k/mu L, P < .001) was higher in the study group. The proportion of patients with maximum CRP >= 100 mg/L was lower in the study group (13.8% vs 29.7% P = .029). The diversity and community composition of the gut microbiota were not significantly different between the 2 groups. Conclusions: Administration of thymosin alpha 1 during and after CCRT was associated with significant reductions in G >= 2 RP and G3 to G4 lymphopenia in patients with LANSCLC compared with historic controls. (C) 2022 Elsevier Inc. All rights reserved.

Automated summary

This study evaluated the efficacy of thymosin alpha 1 in managing radiation pneumonitis in patients with locally advanced non-small cell lung cancer treated with concurrent chemoradiotherapy. The results showed significant reductions in Grade >= 2 radiation pneumonitis and Grade 3 to 4 lymphopenia in patients who received thymosin alpha 1 treatment.