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ePoster Display

1057P - ROS1 mutation can serve- as a potential efficacious predictor of immunotherapy in melanoma patients

Date

16 Sep 2021

Session

ePoster Display

Topics

Tumour Site

Melanoma

Presenters

Hucheng Liu

Citation

Annals of Oncology (2021) 32 (suppl_5): S867-S905. 10.1016/annonc/annonc706

Authors

H. Liu1, J. Zeng1, J. Xiao1, D. Fan2, Y. Chen2, M. Huang3

Author affiliations

  • 1 Department Of Bone Oncology, the First Affiliated Hospital of Nanchang University, 330006 - Nanchang/CN
  • 2 The Medical Department, 3D Medicines Inc., 201100 - Shanghai/CN
  • 3 Medical Marketing Department, 3D Medicines Inc., 201114 - Shanghai/CN
More

Abstract 1057P

Background

Melanoma is a serious skin cancer. Immune checkpoint inhibitors (ICIs) including atezolizumab, pembrolizumab, nivolumab, ipilimumab have shown durable responses and have been approved by FDA. However, ICIs demonstrate antitumor effects only in a fraction of patients, and research exploring the association between gene mutation and clinical benefit is limited. ROS1 mutation rate is high in melanoma. Studies have shown that ROS1 substitutions/indels correlated with higher TMB (Tumor Mutation Burden) and PD-L1+/TMB-H proportions than wild-type genotypes in NSCLC, which means that the mutation of ROS1 gene may be related to the efficacy of immunotherapy in patients with NSCLC, but the association between ROS1 mutation and TMB or survival in melanoma is unknown.

Methods

The association between ROS1 mutation with TMB and survival data was analyzed in melanoma patients from the public immunotherapy-treated cohort called Melanoma.Allen2015.WES.110, which worked as training cohort while the validation cohort1 was retrieved from Pancancer.Samstein2018.NGS.1661 and validation cohort2 was from Melanoma.Hugo2016.WES.38. Wilcoxon test was used for the comparison of TMB. Overall survival (OS) analyses were conducted in the public cohort using Kaplan-Meier curves and log-rank tests. Statistical significance was set at p=0.05.

Results

In the training cohort, 18.2% (20/110) melanoma patients harbored ROS1 mutation. ROS1 mutation is associated with higher TMB (p=0.00002). Survival analysis demonstrates that ROS1 mutation results in significantly longer OS (21.75 vs 7.65 months; HR, 0.55; p=0.046) in melanoma patients treated with ICIs. While the validation cohort1 shows that 20.1% (63/313) melanoma patients harbored ROS1 mutation,which results in an increasing trend on TMB with strongly significant difference (p=1.32*e-17)and significantly longer OS (19 vs 18 months; HR, 0.58; p=0.041). Besides, validation cohort2 also shows that ROS1 mutation results in an higher TMB with significant difference (p=0.017) and significantly longer OS (26.6 vs 14.4 months; HR, 0.25; p=0.045).

Conclusions

This study shows that ROS1 mutation is correlated with higher TMB in melanoma and serves as a predictive biomarker of ICI benefit in melanoma.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

D. Fan: Financial Interests, Personal and Institutional, Member: 3DMed. Inc.. Y. Chen: Financial Interests, Personal and Institutional, Member: 3DMed. Inc.. M. Huang: Financial Interests, Personal and Institutional, Member: 3DMed. Inc.. All other authors have declared no conflicts of interest.

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