Abstract 3291: Development of a novel prognostic scoring system for patient selection in immune checkpoint inhibitor phase 1 clinical trials
Authors: Sen Shiraj , Hess Kenneth , Hong David , Naing Aung , Piha-Paul Sarina , Janku Filip , Fu Siqing , Liu Holly , Jiang Yunfang , Khanji Rahil , Karp Daniel , Tsimberidou Apostolia , Tannir Nizar , Meric-Bernstam Funda , Subbiah Vivek 
Published: July 2017

Abstract
Purpose: To develop a prognostic scoring system for selecting patients for immune checkpoint inhibitor (ICI) phase 1 clinical trials.
Background: The Royal Marsden Hospital (RMH) and MD Anderson (MDA) prognostic scoring systems have been validated for patients in phase 1 clinical trials treated with cytotoxic chemotherapy and targeted therapy, but no such scoring system has been validated to help select patients entering ICI clinical trials.
Methods: We analyzed clinical data from patients treated in phase 1 ICI clinical trials (with anti-CTLA4 and anti-PD1 antibody therapy) at the MD Anderson Center for Targeted Therapy. Sixteen clinical factors were studied. Recursive partitioning analysis identified cut-points for each clinical factor and a Cox proportional hazards regression model was used to identify factors independently affecting overall survival.
Results: Among 172 patients treated with ICI therapy (105 CTLA4-based and 67 PD1-based) between January 2013 and November 2015, the median age was 60 years (range: 19-86 years) and 87 (51%) were male. The most common tumor types treated included renal cell carcinoma (n = 25; 15%), non-small cell lung cancer (n = 21; 12%), melanoma (n = 17; 10%), sarcoma (n = 14; 8%), gastrointestinal stromal tumors (n = 10; 6%), prostate cancer (n = 6; 3%), and colorectal cancer (n = 6; 3%). Seven factors were independently associated with significantly worse overall survival: age &gt;52 years (hazard ratio [HR] 1.59, 95% confidence interval [CI] 1.1-2.4), Eastern Cooperative Oncology Group performance status &gt;1 (HR 2.81, 95% CI 1.3-6.3), lactate dehydrogenase &gt;466 U/L (HR 2.1, 95% CI 1.4-3.2), platelet count &gt;300 × 109/L (HR 1.8, 95% CI 1.2-2.8), absolute neutrophil count &gt;4.9 × 109/L (HR 2.3, 95% CI 1.5-3.5), absolute lymphocyte count &lt;1.8 × 109/L (HR 3.3, 95% CI 1.9-5.7), and liver metastases (HR 1.8, 95% CI 1.2-2.6). An index was created whereby the cohort was divided into four risk groups based on the number of factors present: 0-2, 3, 4, or 5-6. Median overall survival was 24.2 months (0-2), 11.6 months (3), 8.0 months (4), and 3.8 months (5-6); log rank test, p &lt; 0.0001. The Harrell c-index of this scoring system was 0.72, indicating significant predictability.
Conclusion: We have developed a novel “MDA ICI” prognostic scoring system incorporating seven clinical parameters with prognostic significance for patients in phase 1 clinical trials treated with immune checkpoint inhibitors. Unlike in the RMH and MDA prognostic scoring systems, albumin level and number of metastatic sites did not independently correlate with overall survival. Prospective evaluation and external validation of our novel prognostic scoring system is warranted and may help better select patients for future clinical trials of checkpoint inhibitors.
Citation Format: Shiraj Sen, Kenneth Hess, David Hong, Aung Naing, Sarina Piha-Paul, Filip Janku, Siqing Fu, Holly Liu, Yunfang Jiang, Rahil Khanji, Daniel Karp, Apostolia Tsimberidou, Nizar Tannir, Funda Meric-Bernstam, Vivek Subbiah. Development of a novel prognostic scoring system for patient selection in immune checkpoint inhibitor phase 1 clinical trials [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3291. doi:10.1158/1538-7445.AM2017-3291