53 Predictors of response to immune checkpoint inhibitor therapy in metastatic solid tumors: real world evidence. (10th December 2020)

• Record Type: Journal Article
• Authors: Jacob, Aasems; Wu, Jianrong; Kolesar, Jill; Durbin, Eric; Mathew, Aju; Arnold, Susanne; Chauhan, Aman
• Is Part Of: Journal for immunotherapy of cancer. Volume 8(2020)Supplement 3
• Page Start: A33
• Page End: A35
• Publication Date: 2020-12-10
• Subjects: Cancer -- Immunotherapy -- Periodicals; Cancer -- Immunological aspects -- Periodicals; Tumors -- Immunological aspects -- Periodicals; Immunotherapy -- Periodicals; 616.99406105
• DOI: 10.1136/jitc-2020-SITC2020.0053
• Languages: English
• ISSNs: 2051-1426

Abstract

Abstract : Background: Immune checkpoint inhibitor (ICI) therapy is increasingly being used in oncology and novel predictive biomarker for efficacy and side effects are an unmet need. 1 2 The study aims to do a comprehensive analysis of factors affecting outcome from ICI therapy with real-world data and identify potential predictive biomarkers in diverse populations. Methods: We performed a retrospective analysis of patients with metastatic solid tumors who received ICI and underwent molecular profiling with FoundationOne® CDx panel between 2016 and 2020 at Markey Cancer Center, Lexington KY. Progression-free survival (PFS), radiological response, and autoimmune side effects were analyzed and compared with various molecular biomarkers (figure 1 ). Logistic regression, Fisher's exact test, Kaplan-Meier method, log-rank test, and Cox regression were used to analyze clinical features and efficacy outcomes. Results: 69 patients were included in the study (tables 1 and 2 ). 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; table 3 and figure 2 ). This was independent of tumor mutational burden (TMB) status or PDL1 expression status (HR 3.24, p=0.016). PIK3 mutants had a higher overall response rate (ORR) than the wild type (69.6% vs. 43.5%, OR 0.34; p=0.045; tables 3 and 4 ). PIK3 mutants had a higher risk of developing immune-related adverse events (IRAEs) (73.9% vs. 37%, p=0.004). PIK3 mutation did not associate with TMB, PDL1 expression or microsatellite stability status. Median PFS was higher in the high TMB cohort compared to the low-intermediate group and reached statistical significance (median not reached vs. 26 weeks; HR=0.37. 95%CI 0.13, 1.05). PDL1 expression had no significant effect on the radiologic response, but PFS improvement in patients with tumors expressing PDL1 trended towards statistical significance (median 18 vs. 40 weeks. HR=1.43. 95%CI 0.93, 4.46). BRAF mutation conferred shorter PFS (median 17 vs. 39 weeks. HR=0.35. 95%CI 0.14, 0.91) (figure 2 ). Conclusions: High tumor mutational burden and PIK3 mutation conferred better progression-free survival with immunotherapy across cancer types. The improvement in PFS in PIK3 mutated patients was independent of PDL1 status or TMB. The results should prompt further evaluation of these potential biomarkers and more widespread real-world data publications to help determine biomarkers that could benefit specific populations. Ethics Approval: The study was approved by University of Kentucky Institutional Review Board, approval number 49450 References: Topalian SL, Hodi FS, Brahmer JR, et al. Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. N Engl J Med . 2012;366(26):2443–2454. Spencer KR, Wang J, Silk AW, Ganesan S, Kaufman HL, Mehnert JM. Biomarkers for Immunotherapy: Current Developments and Challenges. Am Soc Clin Oncol Educ Book . 2016; 35:e493–503.