Journal article
Real world clinicopathologic observations of patients with metastatic solid tumors receiving immune checkpoint inhibitor therapy: Analysis from Kentucky Cancer Registry
Cancer medicine (Malden, MA), Vol.10(6), pp.2054-2062
03/2021
DOI: 10.1002/cam4.3802
PMCID: PMC7957185
PMID: 33619913
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.
Details
- Title: Subtitle
- Real world clinicopathologic observations of patients with metastatic solid tumors receiving immune checkpoint inhibitor therapy: Analysis from Kentucky Cancer Registry
- Creators
- Aasems Jacob - University of KentuckyJianrong Wu - University of KentuckyJill Kolesar - University of KentuckyEric Durbin - Markey Cancer CenterAju Mathew - University of KentuckySusanne Arnold - University of KentuckyAman Chauhan - University of Kentucky
- Resource Type
- Journal article
- Publication Details
- Cancer medicine (Malden, MA), Vol.10(6), pp.2054-2062
- Publisher
- Wiley
- DOI
- 10.1002/cam4.3802
- PMID
- 33619913
- PMCID
- PMC7957185
- ISSN
- 2045-7634
- eISSN
- 2045-7634
- Number of pages
- 9
- Language
- English
- Date published
- 03/2021
- Academic Unit
- Pharmacy; Pharmaceutical Sciences and Experimental Therapeutics
- Record Identifier
- 9984695795102771
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