1796P - Smoking-related genomic mutation patterns in patients with small cell lung cancer treated in ASTRUM-005 study

Background

Although SCLC is strongly associated with tobacco smoking, few comparison studies on tobacco-smoking-related mutation signature were performed due to the lack of non-smokers in SCLC cohorts. Here we report the results of mutation signature analyses for SCLC patients in ASTRUM-005 trial (NCT04063163) and the relation with their tobacco smoking history.

Methods

ASTRUM-005 was a randomized, double-blind, placebo-controlled, global phase III trial in patients with extensive-stage SCLC. Genomic mutations in 302 patients with available baseline tumor samples were assessed by Med1CDx^TM panel, which included exon region of 601 genes. Two bioinformatic methods, the transversion/transition ratio (TTR) method, and the COSMIC Signature 4 method were applied to analyze tobacco-smoking-related signature. Wilcoxon test was used to calculate the difference among patients with different smoking histories. Clinical data cutoff date was June 13, 2022.

Results

Based on the genomic sequencing data in the 302 patients (current smokers = 69, former smokers = 166, never smokers= 67), no significant differences with different smoking histories were observed by both methods (p value=0.54 and p value=0.38, respectively). To further validate the results, we applied the same analyses on two SCLC cohorts from published paper. Similar results were observed (p >0.05 by all comparisons). We further grouped the patients into high/low TTR groups with median TTR (1.12) as the cutoff value. Higher TTR resulted in shorter median OS (10.0 vs 14.4 mo, HR 1.65) for patients only received chemotherapy, while both groups gained similar benefits for patients received serplulimab plus chemotherapy (14.2 vs 15.9 mo, HR 0.97). Patients showed similar benefits in PFS regardless of the TTR in both treatment groups.

Conclusions

Patients with SCLC showed similar smoking-related genomic mutation patterns regardless of their smoking histories in ASTRUM-005 study. Patients with high TTR might gain less benefit from chemotherapy, suggesting mutations in SCLC might be predictive biomarkers for certain therapies.

Clinical trial identification

NCT04063163.

Editorial acknowledgement

Legal entity responsible for the study

Shanghai Henlius Biotech, Inc.

Funding

Shanghai Henlius Biotech, inc.

Disclosure

M. Jia, X. Yang, M. Chen, F. Yang, C. Hu, Q. Wang, C. Ling, J. Li, Y. Shan, J. Zhu: Financial Interests, Personal, Full or part-time Employment: Shanghai Henlius Biotech, Inc. S. Lechpammer: Financial Interests, Personal, Full or part-time Employment: Fosun Pharma USA. All other authors have declared no conflicts of interest.