1. Baseline mGPS measures reliably predict the prognostic outcome of treatment in patients with metastatic renal cell carcinoma (mRCC)
2. On-treatment mGPS can provide prognostic information before the first radiologic staging and may permit therapy adjustments earlier in the treatment course.
Evidence Rating Level: 1 (Excellent)
Study Rundown: The modified Glasgow prognostic score (mGPS) is a tool to predict response to cancer therapy and is based on C-reactive protein (CRP) and albumin. This study was a post-hoc analysis of two previous studies (IMmotion151 – discovery cohort, and IMmotion150 – validation cohort) investigating whether the mGPS, measured by CRP and albumin and representing long-term systemic inflammatory response, could reliably predict both response and outcomes in patients receiving treatment for metastatic renal cell carcinoma (mRCC). The primary outcome of this study was progression-free survival (PFS) and overall survival (OS). The prognostic value of on-treatment mGPS was compared with radiologic staging. For all baseline mGPS subgroups (low-risk, intermediate-risk, high-risk), on-treatment mGPS was able to predict treatment response or failure. The on-treatment mGPS for all patients in the IMmotion151 study provided a prognostic value with a comparable C-index for OS as IRC-RECIST (Response
Evaluation Criteria in Solid Tumors assessed by the Independent Review Committee) at first staging. In the validation study, IMmotion150, it was found that at 6 weeks post-therapy initiation, on-treatment mGPS permitted prognostication earlier than primary radiology staging, usually completed between 8 and 12 weeks after starting treatment. Limitations to this study include that CRP and albumin are both non-specific inflammatory markers, so confounding factors (e.g., infection, other inflammation) should be considered in future studies. Additionally, the application of on-treatment mGPS has not yet been evaluated in the context of combined treatments (e.g., immune checkpoint inhibitors (ICI) and tyrosine kinase inhibitors (TKI) combination therapy). Overall, the results from this study suggest that applying on-treatment mGPS as part of treatment monitoring for patients receiving therapy for mRCC may improve outcomes and permit earlier treatment adjustments in appropriate patients.
Click to read the study in the JAMA Oncology
In-Depth [randomized controlled trial]: This study was a post-hoc analysis of two randomized clinical trials: the phase 3 IMmotion151 study and the phase 2 IMmotion150 study, a discovery and validation cohort, respectively. These trials each considered the application of the mGPS in the context of mRCC. There were 915 total patients in the IMmotion151 study, 861 of whom had a baseline mGPS recorded and 691 of whom had an on-treatment mGPS available. There were 305 total patients in the IMmotion150 study, 199 of whom had on-treatment mGPS available. In the IMmotion151 study, of the 222 patients categorized at baseline with mGPS as intermediate-risk: 37% improved the on-treatment mGPS to the low-risk category and had a 92.8% OS at one year; 51% of patients remained in this category and had a 74.7% OS at one year; and the remaining 12% were re-classified as high-risk and had a 50.3% OS rate at one year. The baseline high-risk group had only 41 patients and the trends did not reach statistical significance. On-treatment mGPS was reliably able to prognostication treatment response in all baseline mGPS subgroups and provided a prognostic value with a comparable C-index for OS as radiographic assessment at first staging (0.685; 95% confidence interval (CI), 0.638-0.732) vs. 0.690; 95% CI, 0.647-0.733, respectively). Notably, the authors identified a higher-risk mGPS cohort within the radiological disease control subgroup that had more similar OS rates to the progressive disease group (median OS 17.1 vs. 16.1 months). The authors validated the mGPS on-treatment with similar discriminative predictive abilities using the IMmotion150 Validation Cohort. This study provides validation of a predictive score of current mRCC therapies that may provide additional insight into how patients are responding to their cancer therapies.
Image: PD
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