Real world clinicopathologic observations of patients with metastatic solid tumors receiving immune checkpoint inhibitor therapy: Analysis from Kentucky Cancer Registry
Abstract The state of Kentucky has the highest cancer incidence and mortality in the United States. High‐risk populations such as this are often underrepresented in clinical trials. The study aims to do a comprehensive analysis of molecular landscape of metastatic cancers among these patients with d...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2021-03-01
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| Series: | Cancer Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/cam4.3802 |
| _version_ | 1819158215157350400 |
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| author | Aasems Jacob Jianrong Wu Jill Kolesar Eric Durbin Aju Mathew Susanne Arnold Aman Chauhan |
| author_facet | Aasems Jacob Jianrong Wu Jill Kolesar Eric Durbin Aju Mathew Susanne Arnold Aman Chauhan |
| author_sort | Aasems Jacob |
| collection | DOAJ |
| description | Abstract The state of Kentucky has the highest cancer incidence and mortality in the United States. High‐risk populations such as this are often underrepresented in clinical trials. The study aims to do a comprehensive analysis of molecular landscape of metastatic cancers among these patients with detailed evaluation of factors affecting response and outcomes to immune checkpoint inhibitor (ICI) therapy. We performed a retrospective analysis of metastatic solid tumor patients who received ICI and underwent molecular profiling at our institution. Sixty nine patients with metastatic solid tumors who received ICI were included in the study. Prevalence of smoking and secondhand tobacco exposure was 78.3% and 14.5%, respectively. TP53 (62.3%), CDKN1B/2A (40.5%), NOTCH and PIK3 (33.3%) were the most common alterations in tumors. 67.4% were PDL1 positive and 59.4% had intermediate‐high tumor mutational burden (TMB). Median TMB (12.6) was twofold to fourfold compared to clinical trials. The prevalence of mutations associated with smoking, homologous recombinant repair and PIK3/AKT/mTOR pathway mutations was higher compared to historic cohorts. PDL1 expression had no significant effect on radiologic response, but PFS improvement in patients with tumors expressing PDL1 trended toward statistical significance (median 18 vs. 40 weeks. HR = 1.43. 95%CI 0.93, 4.46). Median PFS was higher in the high‐TMB cohort compared to low‐intermediate TMB (median not reached vs. 26 weeks; HR = 0.37. 95%CI 0.13, 1.05). A statistically significant improvement in PFS was observed in the PIK3 mutated cohort (median 123 vs. 23 weeks. HR = 2.51. 95%CI 1.23, 5.14). This was independent of tumor mutational burden (TMB) status or PDL1 expression status. PIK3 mutants had a higher overall response rate than the wild type (69.6% vs. 43.5%, OR 0.34; p = 0.045). The results should prompt further evaluation of these potential biomarkers and more widespread real‐world data publications which might help determine biomarkers that could benefit specific populations. |
| first_indexed | 2024-12-22T16:21:07Z |
| format | Article |
| id | doaj.art-d61ab1173d834cb0be5234476e25a008 |
| institution | Directory Open Access Journal |
| issn | 2045-7634 |
| language | English |
| last_indexed | 2024-12-22T16:21:07Z |
| publishDate | 2021-03-01 |
| publisher | Wiley |
| record_format | Article |
| series | Cancer Medicine |
| spelling | doaj.art-d61ab1173d834cb0be5234476e25a0082022-12-21T18:20:14ZengWileyCancer Medicine2045-76342021-03-011062054206210.1002/cam4.3802Real world clinicopathologic observations of patients with metastatic solid tumors receiving immune checkpoint inhibitor therapy: Analysis from Kentucky Cancer RegistryAasems Jacob0Jianrong Wu1Jill Kolesar2Eric Durbin3Aju Mathew4Susanne Arnold5Aman Chauhan6Department of Internal Medicine University of Kentucky Lexington KY USADepartment of Biostatistics University of Kentucky Lexington KY USACollege of Pharmacy University of Kentucky Lexington KY USACancer Research Informatics Shared Resource Facility Markey Cancer Center University of Kentucky Lexington KY USADepartment of Internal Medicine University of Kentucky Lexington KY USADepartment of Internal Medicine University of Kentucky Lexington KY USADepartment of Internal Medicine University of Kentucky Lexington KY USAAbstract The state of Kentucky has the highest cancer incidence and mortality in the United States. High‐risk populations such as this are often underrepresented in clinical trials. The study aims to do a comprehensive analysis of molecular landscape of metastatic cancers among these patients with detailed evaluation of factors affecting response and outcomes to immune checkpoint inhibitor (ICI) therapy. We performed a retrospective analysis of metastatic solid tumor patients who received ICI and underwent molecular profiling at our institution. Sixty nine patients with metastatic solid tumors who received ICI were included in the study. Prevalence of smoking and secondhand tobacco exposure was 78.3% and 14.5%, respectively. TP53 (62.3%), CDKN1B/2A (40.5%), NOTCH and PIK3 (33.3%) were the most common alterations in tumors. 67.4% were PDL1 positive and 59.4% had intermediate‐high tumor mutational burden (TMB). Median TMB (12.6) was twofold to fourfold compared to clinical trials. The prevalence of mutations associated with smoking, homologous recombinant repair and PIK3/AKT/mTOR pathway mutations was higher compared to historic cohorts. PDL1 expression had no significant effect on radiologic response, but PFS improvement in patients with tumors expressing PDL1 trended toward statistical significance (median 18 vs. 40 weeks. HR = 1.43. 95%CI 0.93, 4.46). Median PFS was higher in the high‐TMB cohort compared to low‐intermediate TMB (median not reached vs. 26 weeks; HR = 0.37. 95%CI 0.13, 1.05). A statistically significant improvement in PFS was observed in the PIK3 mutated cohort (median 123 vs. 23 weeks. HR = 2.51. 95%CI 1.23, 5.14). This was independent of tumor mutational burden (TMB) status or PDL1 expression status. PIK3 mutants had a higher overall response rate than the wild type (69.6% vs. 43.5%, OR 0.34; p = 0.045). The results should prompt further evaluation of these potential biomarkers and more widespread real‐world data publications which might help determine biomarkers that could benefit specific populations.https://doi.org/10.1002/cam4.3802biomarkersimmune checkpoint inhibitorsimmunotherapyimmunotherapy responsesolid tumors |
| spellingShingle | Aasems Jacob Jianrong Wu Jill Kolesar Eric Durbin Aju Mathew Susanne Arnold Aman Chauhan Real world clinicopathologic observations of patients with metastatic solid tumors receiving immune checkpoint inhibitor therapy: Analysis from Kentucky Cancer Registry Cancer Medicine biomarkers immune checkpoint inhibitors immunotherapy immunotherapy response solid tumors |
| title | Real world clinicopathologic observations of patients with metastatic solid tumors receiving immune checkpoint inhibitor therapy: Analysis from Kentucky Cancer Registry |
| title_full | Real world clinicopathologic observations of patients with metastatic solid tumors receiving immune checkpoint inhibitor therapy: Analysis from Kentucky Cancer Registry |
| title_fullStr | Real world clinicopathologic observations of patients with metastatic solid tumors receiving immune checkpoint inhibitor therapy: Analysis from Kentucky Cancer Registry |
| title_full_unstemmed | Real world clinicopathologic observations of patients with metastatic solid tumors receiving immune checkpoint inhibitor therapy: Analysis from Kentucky Cancer Registry |
| title_short | Real world clinicopathologic observations of patients with metastatic solid tumors receiving immune checkpoint inhibitor therapy: Analysis from Kentucky Cancer Registry |
| title_sort | real world clinicopathologic observations of patients with metastatic solid tumors receiving immune checkpoint inhibitor therapy analysis from kentucky cancer registry |
| topic | biomarkers immune checkpoint inhibitors immunotherapy immunotherapy response solid tumors |
| url | https://doi.org/10.1002/cam4.3802 |
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