Integrating On-Treatment Modified Glasgow Prognostic Score and Imaging to Predict Response and Outcomes in Metastatic Renal Cell Carcinoma

IMPORTANCE: In the era of immuno-oncology, imaging alone seems to be insufficient to capture treatment responses, as patients with stable disease treated with immunotherapy have a wide range of clinical outcomes. There is an unmet need for complementary (ideally cost-efficient) markers that enable assessment of therapy response and outcomes in conjunction with imaging. OBJECTIVES: To examine whether longitudinal changes in the modified Glasgow prognostic score (mGPS), which is based on C-reactive protein and albumin, can predict responses and outcomes in patients with metastatic renal cell carcinoma (mRCC). DESIGN, SETTING, AND PARTICIPANTS: This post hoc analysis, conducted from October 2022 to April 2023, evaluated the prognostic and predictive performance of on-treatment mGPS in patients with mRCC being treated with atezolizumab (plus bevacizumab) or sunitinib in 2 randomized clinical trials: the phase 3 IMmotion151 study (discovery cohort) and the phase 2 IMmotion150 study (validation cohort). MAIN OUTCOMES AND MEASURES: Outcomes were investigator-assessed progression-free survival (PFS) per Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1 and overall survival (OS) for survival analyses. To compare the prognostic value of the on-treatment mGPS with radiologic staging, we used RECIST assessed by the Independent Review Committee (IRC-RECIST) to ensure high data quality. RESULTS: Of the 915 patients with mRCC in the IMmotion151 discovery cohort, baseline mGPS was available for 861 patients and on-treatment mGPS for 691. The IMmotion150 validation cohort included 305 patients with mRCC, and on-treatment mGPS could be evaluated for 199. In the IMmotion150 study, on-treatment mGPS predicted outcomes as early as 6 weeks following therapy initiation, thereby opening a window for early therapy adjustments. In both clinical trials, on-treatment mGPS provided valuable prognostic information regardless of imaging-assessed treatment response at first staging. Of note, in the disease control subgroup, on-treatment mGPS exhibited superior and independent prognostic information compared with IRC-RECIST (available for 611 patients; C-index, 0.651 [95% CI, 0.588-0.714] for the mGPS during treatment vs 0.574 [95% CI, 0.528-0.619] for IRC-RECIST). CONCLUSIONS AND RELEVANCE: These data support the concept of integrating on-treatment mGPS for more holistic and patient-centered therapy monitoring in addition to radiologic staging to improve clinical care at a low cost for patients with mRCC.