Lead Investigator: Jörg Ellinger, University Hospital Bonn
Title of Proposal Research: Evaluation of the performance of the modified Glasgow prognostic score in urothelial carcinoma, non-small cell lung cancer and renal cell carcinoma
Vivli Data Request: 7797
Funding Source: None
Potential Conflicts of Interest: None
Summary of the Proposed Research:
Urothelial carcinoma or bladder cancer (UC) is a common disease that affects about 80000 people and kills 17000 in the US each year. Non-small cell lung cancer (NSCLC) is one of the most common cancers with more than 236000 new cases diagnosed each year in the US and more than 130000 deaths. Renal cell carcinoma (RCC) or kidney cancer (renal = kidney) is also one of the most common malignancies worldwide, affecting about 80000 people and killing about 14000 people in the US each year.
These cancers are preferably removed by surgery, however, if the tumor has spread in the body (metastatic disease), patients need a systemic treatment.
In the last years, immune-checkpoint inhibition (ICI) has evolved as a promising treatment approach. It works by enabling the patient´s immune system to attack and kill the tumor. This is achieved by blocking signals on the tumor cells that prevent the immune system from attacking the cells, these signals are called immune checkpoints. However, not every patient profits from ICI. Thus, it is important to identify patients who are candidates for this kind of treatment.
The modified Glasgow prognostic score (mGPS) is a score based on two different laboratory parameters (albumin and C reactive protein) that can be measured in any routine blood draw. It has been shown to be able to yield information on prognosis of patients with different cancers, such as UC, NSCLC and RCC. However, it has not been validated in a prospective study on ICI-treated patients with UC and NSCLC (meaning the data was collected in a standardized, structured manner). In the proposed study the mGPS will be validated in a prospective trial including patients with metastatic bladder cancer (IMvigor211) and lung cancer (NCT02008227).
As part of a currently ongoing research project (Vivli ID: 00007164), we demonstrated that the mGPS outperforms the international metastatic RCC database consortium (IMDC) score, the current clinical standard for risk stratification for patients with metastatic kidney cancer prior start of oncological treatment. In the past, immunotherapy was only used for patients with metastatic kidney cancer. To date, there is growing evidence for the advantages of adjuvant therapy in non-metastatic high-risk kidney cancer (i.e. after surgical removal of the tumor to prevent recurrence). There is currently no way to identify patients that will profit from this treatment. This study aims to validate the mGPS in patients receiving adjuvant therapy for high-risk kidney cancer (S-TRAC and ASSURE).
This study will help to more precisely predict an individual patient´s risk and thereby add an important tool for clinicians to inform the choice of treatment.
Statistical Analysis Plan:
In this research proposal, we aim to investigate the prognostic significance of mGPS in patients with mUC and NSCLC treated with atezolizumab versus chemotherapy in the indicated study cohorts (Powles et al. Atezolizumab versus chemotherapy in patients with platinum-treated locally advanced or metastatic urothelial carcinoma (IMvigor211): a multicentre, open-label, phase 3 randomised controlled trial. The Lancet 2018; Rittmeyer A et al. Atezolizumab versus docetaxel in patients with previously treated non-small-cell lung cancer (OAK): a phase 3, open-label, multicentre randomised controlled trial. The Lancet. 2017)
Further, we want to investigate the prognostic value of mGPS for patients with kidney cancer treated with nephrectomy using the adjuvant studies S-TRAC and ASSURE.
In the research project with Vivli ID: 00007164, we have already shown that the mGPS has a strong prognostic value for patients with metastatic RCC under oncological therapy. In the S-TRAC and ASSURE trial cohorts for adjuvant treatment with tyrosine kinase inhibitors, we are particularly interested in the placebo-controlled subgroup, as these patients at high risk for recurrence represent a currently interesting clinical patient group for whom adjuvant ICB has now recently been approved.
Patients with missing data will be excluded.
The mGPS is determined by assigning one point for an elevated serum C-reactive protein (CRP) concentration of > 10 mg/L and a second point for decreased serum albumin (< 3.5 g/dL) only in patients with elevated CRP. Patients are then stratified into low (mGPS=0), intermediate (mGPS=1), and high risk (mGPS=2).
Fisher’s exact, Mann–Whitney U, and Kruskal–Wallis tests will be applied to perform intergroup comparisons. The progression-free
(PFS) and overall survival (OS), including 95% confidence intervals will be estimated with the Kaplan–Meier method and compared with log-rank tests. To compare mGPS risk groups, baseline patient (age, gender, ethnicity, Karnofsky Index) and tumor-related parameters (e.g. histology, PD-L1 expression, previous surgery) on OS and PFS, univariate and multiple Cox regressions will be conducted. Independent variables will only be included in the multiple regression if the respective effect is significant in the univariate analysis; Forward Wald selection will be applied. Statistical analyses will be performed R-Studio via the vivli research environment as previously performed for Vivli ID: 00007164. All statistical tests will be two-sided, and p-values < 0.05 will be considered significant.
Requested Studies:
A Phase III, Open-Label, Multicenter, Randomized Study to Investigate the Efficacy and Safety of Atezolizumab (Anti-PD-L1 Antibody) Compared With Chemotherapy in Patients With Locally Advanced or Metastatic Urothelial Bladder Cancer After Failure With Platinum-Containing Chemotherapy
Data Contributor: Roche
Study ID: NCT02302807
Sponsor ID: GO29294
A Phase III, Open-Label, Multicenter, Randomized Study to Investigate the Efficacy and Safety of Atezolizumab (Anti-PD-L1 Antibody) Compared With Docetaxel in Patients With Non-Small Cell Lung Cancer After Failure With Platinum Containing Chemotherapy
Data Contributor: Roche
Study ID: NCT02008227
Sponsor ID: GO28915
Sunitinib Treatment Of Renal Adjuvant Cancer (S-trac): A Randomized Double-blind Phase 3 Study Of Adjuvant Sunitinib Vs. Placebo In Subjects At High Risk Of Recurrent Rcc
Data Contributor: Pfizer Inc.
Study ID: NCT00375674
Sponsor ID: A6181109
ASSURE: Adjuvant Sorafenib or Sunitinib for Unfavorable Renal Carcinoma
Data Contributor: Project Data Sphere
Study ID: NCT00326898
Sponsor ID: NCI-2009-00534
A Phase II, Randomized Study of Atezolizumab (Anti-PD-L1 Antibody) Administered as Monotherapy or in Combination With Bevacizumab Versus Sunitinib in Patients With Untreated Advanced Renal Cell Carcinoma
Data Contributor: Roche
Study ID: NCT01984242
Sponsor ID: WO29074
A Phase II, Multicenter, Single-Arm Study of Atezolizumab in Patients With Locally Advanced or Metastatic Urothelial Bladder Cancer
Data Contributor: Roche
Study ID: NCT02951767
Sponsor ID: GO29293 (Cohort 1)
A Phase II, Multicenter, Single-Arm Study of Atezolizumab in Patients With Locally Advanced or Metastatic Urothelial Bladder Cancer
Data Contributor: Roche
Study ID: NCT02108652
Sponsor ID: GO29293 (Cohort 2)
Public Disclosures:
Jonas Saal, Tobias Bald, Markus Eckstein, Manuel Ritter, Peter Brossart, Jörg Ellinger, Michael Hölzel, Niklas Klümper. Early CRP kinetics predicts immunotherapy response in NSCLC in the phase III OAK trial. JNCI Cancer Spectrum, 2023;, pkad027. doi: 10.1093/jncics/pkad027