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

ABSTRACT:

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?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?P?P?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.

SUBMITTER: Day D 

PROVIDER: S-EPMC7050022 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature