Survival in Early Phase Immuno-Oncology Trials: Development and Validation of a Prognostic Index

BACKGROUND: Immuno-oncology (IO) is rapidly evolving in early drug development. We aimed to develop and prospectively validate a prognostic index for patients treated in IO phase I trials to assist with patient selection. METHODS: The development cohort included 192 advanced solid tumor patients tre...

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Detalles Bibliográficos
Autores principales: Day, Daphne, Guo, Christina, Kanjanapan, Yada, Tran, Ben, Spreafico, Anna, Joshua, Anthony M, Wang, Lisa, Abdul Razak, Albiruni R, Leighl, Natasha B, Hansen, Aaron R, Butler, Marcus O, Siu, Lillian L, Desai, Jayesh, Bedard, Philippe L
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2019
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7050022/
https://www.ncbi.nlm.nih.gov/pubmed/32337489
http://dx.doi.org/10.1093/jncics/pkz071
Descripción
Sumario:BACKGROUND: Immuno-oncology (IO) is rapidly evolving in early drug development. We aimed to develop and prospectively validate a prognostic index for patients treated in IO phase I trials to assist with patient selection. METHODS: The development cohort included 192 advanced solid tumor patients treated in 13 IO phase I trials, targeting immune checkpoint and/or co-stimulatory molecules. A prognostic scoring system was developed from multivariate survival analysis of 10 clinical factors, and subsequently validated in two independent validation cohorts (n = 152 and n = 80). RESULTS: In the development cohort, median age was 57.5 years (range = 20.4–84.8 years). Median progression-free survival and overall survival (OS) were 13.4 and 73.6 weeks, respectively, 90-day mortality was 16%, and overall response rate was 20%. In multivariate analysis, Eastern Cooperative Oncology Group performance status greater than or equal to 1 (hazard ratio [HR] = 3.2, 95% confidence interval [CI] = 1.8 to 5.7; P < .001), number of metastatic sites greater than 2 (HR = 2.0, 95% CI = 1.3 to 3.1; P = .003), and albumin less than the lower limit of normal (HR = 1.8, 95% CI = 1.2 to 2.7; P = .007) were independent prognostic factors; comprising the Princess Margaret Immuno-oncology Prognostic Index (PM-IPI). Patients with a score of 2–3 compared with patients with a score of 0–1 had shorter OS (HR = 3.4, 95% CI = 1.9 to 6.1; P < .001), progression-free survival (HR = 2.3, 95% CI = 1.7 to 3.2; P < .001), higher 90-day mortality (odds ratio = 8.1, 95% CI = 3.0 to 35.4; P < .001), and lower overall response rate (odds ratio = 0.4, 95% CI = 0.2 to 0.8; P = .019). The PM-IPI retained prognostic ability in both validation cohorts and performed better than previously published phase I prognostic scores for predicting OS in all three cohorts. CONCLUSIONS: The PM-IPI is a validated prognostic score for patients treated in phase I IO trials and may aid in improving patient selection.

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