Development of a prognostic scoring system for patients with advanced cancer enrolled in immune checkpoint inhibitor phase 1 clinical trials

Background: We sought to develop a prognostic scoring system to aid in patient selection for immune checkpoint inhibitor (ICI) phase 1 clinical trials. Methods: Clinical data from patients treated in phase 1 ICI clinical trials at MD Anderson (MDA) Center were analysed. Seventeen clinical factors were studied. Recursive partitioning analysis, a tree-based model, was used to develop a regression tree and identify optimal cut-points based on differences in survival for each clinical factor. A Cox proportional hazards regression model was then used to identify factors independently affecting overall survival. A prognostic scoring system was subsequently developed. Results: A total of 172 patients (105 CTLA4- and 67 PD1-based) were analysed. Seven factors were independently associated with worse overall survival (OS): age > 52 years (hazard ratio (HR) 1.59, 95% confidence interval (CI) 1.1-2.4), Eastern Cooperative Oncology Group performance status > 1 (HR 2.81, 95%CI 1.3-6.3), lactate dehydrogenase >466 (which is 0.75 x the upper limit of normal at our institution) (HR 2.1, 95% CI 1.4-3.2), platelet count >300 x 10(3) mu L-1 (HR 1.8, 95% CI 1.2-2.8), absolute neutrophil count >4.9 x 10(3) mu L-1 (HR 2.3, 95% CI 1.5-3.5), absolute lymphocyte count <1.8 x 103 mu L-1 (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 by dividing the cohort into risk groups based on the number of factors present: 0-2, 3, 4, or 5-6. Median OS was 24.2 months, 11.6 months, 8.0 months, and 3.8 months for patients with 0-2, 3, 4, or 5-6 risk factors, respectively; log-rank test, P<0.0001. The Harrell c-index of this scoring system was 0.72, indicating better predictability than the Royal Marsden Hospital score (c-index 0.67) and MDA score (c-index 0.61). Conclusions: We have developed a novel MDA-ICI prognostic scoring system for patients treated in phase 1 ICI clinical trials. Prospective evaluation and external validation is warranted and may help aid patient selection for future clinical trials.