Thymalfasin Boosts Survival in Advanced Lung Cancer When Added to Immunotherapy

Lung cancer is the leading cause of cancer death in China, with over one million new cases annually. For patients with advanced, driver gene-negative non-small cell lung cancer (NSCLC), immune checkpoint inhibitors (ICIs) targeting PD-1/PD-L1 have transformed treatment, but durable responses occur in only 10–40% of patients. Thymalfasin (Thymosin α1), a 28-amino acid immunomodulatory peptide, promotes T-cell differentiation, enhances dendritic cell antigen presentation, and has shown synergistic antitumor activity in preclinical and early clinical settings. This retrospective study asked whether adding thymalfasin to different ICI-based regimens could improve outcomes in real-world NSCLC patients.

Researchers at Shijiazhuang People's Hospital enrolled 120 eligible patients treated between January 2021 and December 2024. Patients were divided into three groups based on their actual first-line regimen: Group A (n=42) received platinum-based doublet chemotherapy plus ICIs plus thymalfasin; Group B (n=44) received single-agent chemotherapy plus ICIs plus thymalfasin; Group C (n=34) received ICIs plus thymalfasin only. ICIs used included pembrolizumab, sintilimab, camrelizumab, and tislelizumab. Thymalfasin was administered subcutaneously at 1.6 mg twice weekly throughout treatment. Baseline characteristics — including age, sex, TNM stage, pathological type, ECOG performance status, and PD-L1 expression — were well balanced across groups (all P>0.05).

For tumor response, no complete responses were observed in any group. Partial response rates were 11.90% (Group A), 9.09% (Group B), and 5.88% (Group C), with stable disease in 83.34%, 84.09%, and 82.35%, respectively. Objective response rate (ORR) and disease control rate (DCR) did not differ significantly among groups (P>0.05). However, survival outcomes diverged meaningfully: both Groups A and B demonstrated significantly longer median progression-free survival (PFS) and overall survival (OS) compared with Group C (P<0.05 for both), while Groups A and B did not differ significantly from each other. This suggests that the addition of any chemotherapy backbone to ICI plus thymalfasin confers a meaningful survival advantage over immunotherapy-thymalfasin alone.

Immunological assessments at six months post-treatment revealed significant improvements in CD3+, CD4+, and CD4+/CD8+ ratios, as well as immunoglobulins IgG, IgM, and IgA across all groups (all P<0.05). Group A showed the most pronounced increases in CD4+ T-cell counts, IgG, and IgA levels compared with Group C (P<0.05). Quality of life, measured by the FACT-L questionnaire, improved most in Group A (P<0.05), and the decline in 6-minute walk distance (6MWD) was smallest in Group A (P<0.05), indicating better preserved functional capacity. Adverse events — including myelosuppression, gastrointestinal reactions, fatigue, hepatic/renal impairment, and rash/alopecia — were comparable across all three groups (all P>0.05), suggesting thymalfasin does not amplify treatment toxicity.

The study has notable limitations. Its retrospective, single-center design introduces selection bias, and no control arm without thymalfasin was included, making it impossible to isolate thymalfasin's independent contribution. Sample sizes, particularly in Group C (n=34), were modest. Nonetheless, the findings support thymalfasin as a potentially valuable adjunct to chemoimmunotherapy in advanced NSCLC, warranting prospective randomized trials to confirm these signals.