We now have an aging population of cancer patients, resulting in a frailer oncological cohort. The increased prevalence of comorbidities can complicate treatment. Therefore, it is important to carefully embed validated prognostic models into our personalised risk stratification and patient selection strategy to avoid exposure to unnecessary immunotoxicities. These models often incorporate a range of clinical and laboratory parameters, such as age, weight, cognition, nutritional status, performance status, haemoglobin, calcium, and neutrophil-to-lymphocyte ratio (NLR), among others. Our study aligns with the agenda of precision cancer medicine and helps us to improve patient survival and response rates.
The European Society for Medical Oncology guidelines advocate for the use of prognostic models in renal cell carcinoma (RCC), such as the International Metastatic Renal Cancer Database Consortium (IMDC) score for advanced RCC. However, the IMDC score was validated at a time when tyrosine kinase inhibitors were more widely used as the first-line treatment option rather than immunotherapy, where its prognostic value is now unclear.1
The Geriatric 8 (G8) score was designed to identify older cancer patients who may benefit from a comprehensive geriatric assessment (CGA) and has been shown to amplify the predictive value of the ECOG performance status scale.2 The Meet-URO score, a novel and cost-effective composite clinical prognostic score, includes two other biomarkers, the pre-treatment NLR and bony metastases, into the IMDC score to formulate a risk stratification tool. Our study has also shown that it holds prognostic value for predicting both overall survival (OS) and progression-free survival (PFS) and hence can be utilized to guide key immunotherapy decisions.3
Overview of the study
The aim of this research study is to evaluate the prognostic role of the G8 screening tool within the context of the Meet-URO classification against the backdrop of the evolving metastatic RCC treatment landscape. We retrospectively evaluated 106 patients receiving first-line immuno-combination nivolumab and ipilimumab. Data were collected from the Italian Expanded Access Program (EAP) across 85 centers between April and October 2019. The primary endpoint was OS, defined as duration from first administration of Nivolumab to death, and the secondary endpoint was PFS, measured from the initiation of Nivolumab to the earliest instance of disease progression or death.
Critical analysis
OS was longer in the G8 >14 population compared to the G8 ≤14 group, consistent with the fact that the G8 >14 group generally has better health status (1-year 76.1% vs 58.6%, p = 0.006). There was no statistically significant difference in PFS between the G8 >14 and G8 ≤14 groups (1-year 46.2% vs 29.3%, p = 0.2). The G8 score has previously been validated as a screening tool to identify which cancer patients aged above 70 require a CGA before initiation of treatment.4 Interestingly, in our subgroup aged 70 and above, neither PFS nor OS showed significant differences according to the G8 score (p = 0.3 for both). Importantly, the Meet-URO model was significantly prognostic for both PFS (p = 0.001) and OS (p = 0.001) in the overall population and for OS only (p = 0.02) in the over 70 cohort.
Significant differences between the G8 populations were observed within the IMDC model. When compared to G8 ≤14, G8 scores >14 were associated with more intermediate risk (83.3% vs 56.3%) and less poor risk IMDC groups (16.7% vs 43.8%) [p = 0.007]. Similarly, although with borderline statistical significance, the Meet-URO score risk groups were different, with better G8 scores associated with lower risk categories (p = 0.05). There was also a significant difference identified in NLR values between the G8 groups (p = 0.04). Higher NLR values were associated with worse G8 scores (≤14) (60.9% with NLR ≥ 3.2 vs 38.1% in the G8 ≤ 14 vs G8 > 14, respectively).
Implications and future directions
These results demonstrate the prognostic value of the G8 score for OS in the overall metastatic RCC population receiving first-line ipilimumab-nivolumab, while the Meet-URO score shows consistent prognostic ability for both PFS and OS across different age groups.
We need to have more prospective studies with larger patient cohorts, including other demographic and ethnic groups. The Meet-URO 33 study is ongoing and will help to further refine our conclusions, as analyses on the G8 score will be conducted on a larger scale, and other prognostic factors for mRCC will also be investigated as part of the study. It aims to provide further survival and toxicity data for the various different immuno-combinations.5
Written by: Ria Nagpal, MB, BCh, BAO, MRCP(UK), Portsmouth Hospitals University NHS Trust, Portsmouth, United Kingdom
References
- Powles T, Albiges L, Bex A, et al. Renal cell carcinoma: ESMO clinical practice guideline for diagnosis, treatment and follow-up. Ann Oncol. 2024;35(8):692-706.
- Takahashi M, Takahashi M, Komine K, et al. The G8 screening tool enhances prognostic value to ECOG performance status in elderly cancer patients: A retrospective, single institutional study. PLoS One. 2017;12(6):e0179694. Published 2017 Jun 22.
- Rebuzzi SE, Signori A, Buti S, et al. Validation of the Meet-URO score in patients with metastatic renal cell carcinoma receiving first-line nivolumab and ipilimumab in the Italian expanded access program. ESMO Open. 2022;7(6):100634.
- Soubeyran P, Bellera C, Goyard J, et al. Screening for vulnerability in older cancer patients: The ONCODAGE prospective multicenter cohort study. PLoS One. 2014;9(12):e115060. Published 2014 Dec 11.
- Rebuzzi SE, Fornarini G, Signori A, et al. International multicenter real-world REGistry for patients with metastatic renAL cell carcinoma - Meet-URO 33 study (REGAL study). BMC Cancer. 2024;24(1):757. Published 2024 Jun 24.