Oncogenic Pathway Alterations Were Correlated with Tumor Progression and Survival Benefits from Immunotherapy in Lung Adenocarcinoma
Presented During:
Sunday, May 7, 2023: 8:00AM - 8:15AM
Los Angeles Convention Center
Posted Room Name:
408B
Abstract No:
104
Submission Type:
Abstract Submission
Authors:
Fangqiu Fu (1), Yang Zhang (1), Haiquan Chen (1)
Institutions:
(1) Fudan University Shanghai Cancer Center, Shanghai, Shanghai
Submitting Author:
Fangqiu Fu
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Fudan University Shanghai Cancer Center
Fudan University Shanghai Cancer Center
Co-Author(s):
Yang Zhang
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Fudan University Shanghai Cancer Center
Fudan University Shanghai Cancer Center
*Haiquan Chen
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Fudan University Shanghai Cancer Center
Fudan University Shanghai Cancer Center
Presenting Author:
Fangqiu Fu
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Fudan Shanghai Cancer Center
Fudan Shanghai Cancer Center
Abstract:
Objective: Oncogenic pathway alterations contribute to tumor progression in lung adenocarcinoma. The study aims to test whether number of oncogenic pathway alterations (NPA) could predict clinical outcomes in surgically-resected lung adenocarcinoma and efficacy of immunotherapy.
Methods: We calculated NPA for each patient with lung adenocarcinoma from our two prospective cohorts with available DNA sequencing data (250 patients receiving 520-gene target sequencing and 99 patients receiving whole-exome sequencing). Two public cohorts from MSKCC and POPLAR/OAK were utilized to explore the predictive value of NPA in the efficacy of immunotherapy. A pathway was considered to be "altered" if at least one nonsynonymous mutation from this pathway was discovered.
Results: Among patients having panel sequencing, the most prevalent pathway alteration was RTK/RAS, appearing in 98.4% of the whole cohort (Figure 1A). Increased NPA was associated with larger TMB (P < 0.001) and tumor size (P < 0.001). High-grade adenocarcinoma (P < 0.001), visceral pleural invasion (P = 0.063), advanced TNM stage (P < 0.001), and high expression of PD-L1 (P = 0.033) were more common in patients with higher NPA. Survival analyses of patients receiving whole-exome sequencing demonstrated patients with larger NPA had significantly worse recurrence-free survival (P = 0.007) and overall survival (P < 0.001). Furthermore, high NPA was associated improved survival in the MSKCC cohort receiving immunotherapy (Figure 1B). Combination of NPA and tumor mutation burden provided better performance in identifying patients benefitting from immunotherapy in the POPLAR&OAK cohort (Figure 1C).
Conclusions: Increased NPA was associated with advanced TNM stage and poor survival in lung adenocarcinoma. NPA was a novel predictor of efficacy to immunotherapy.
Methods: We calculated NPA for each patient with lung adenocarcinoma from our two prospective cohorts with available DNA sequencing data (250 patients receiving 520-gene target sequencing and 99 patients receiving whole-exome sequencing). Two public cohorts from MSKCC and POPLAR/OAK were utilized to explore the predictive value of NPA in the efficacy of immunotherapy. A pathway was considered to be "altered" if at least one nonsynonymous mutation from this pathway was discovered.
Results: Among patients having panel sequencing, the most prevalent pathway alteration was RTK/RAS, appearing in 98.4% of the whole cohort (Figure 1A). Increased NPA was associated with larger TMB (P < 0.001) and tumor size (P < 0.001). High-grade adenocarcinoma (P < 0.001), visceral pleural invasion (P = 0.063), advanced TNM stage (P < 0.001), and high expression of PD-L1 (P = 0.033) were more common in patients with higher NPA. Survival analyses of patients receiving whole-exome sequencing demonstrated patients with larger NPA had significantly worse recurrence-free survival (P = 0.007) and overall survival (P < 0.001). Furthermore, high NPA was associated improved survival in the MSKCC cohort receiving immunotherapy (Figure 1B). Combination of NPA and tumor mutation burden provided better performance in identifying patients benefitting from immunotherapy in the POPLAR&OAK cohort (Figure 1C).
Conclusions: Increased NPA was associated with advanced TNM stage and poor survival in lung adenocarcinoma. NPA was a novel predictor of efficacy to immunotherapy.
Categories:
Lung Cancer
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