Objective: First-line immune-combination therapy based on immune checkpoint inhibitors (ICIs) and tyrosine kinase inhibitors (TKIs) are the new mainstay in metastatic renal cell cancer (mRCC). In this setting, there is a dearth of standard prognostic/predictive parameters to guide treatment choice. The novel prognostic Meet-URO score (IMDC score + bone metastases and neutrophil-to-lymphocyte ratio - NLR) showed a higher prognostic accuracy than IMDC in 306 patients on first-line nivolumab + ipilimumab in the Italian Expanded Access Program (PMID: 36493602). Hence, the necessity to externally validate and expand to other first-line immune-combination settings. Methods: Twenty-seven European centres were included. Baseline patient and tumour characteristics were collected, including the IMDC score along with the presence of pre-treatment bone metastases, neutrophils, and lymphocytes for calculating the Meet-URO score. The prognostic performance of Meet-URO and IMDC scores were compared and defined by the Harrell’s c-index. Results: 1174 mRCC patient data was retrospectively collected. The median age was 64. 72.8% were male, 54.2% received nephrectomy, 62% were metastatic at diagnosis and 86.7% had clear-cell histology. 35% had bone metastases and 51.6% had NLR ⩾ 3.2. 672 (57.2%) patients received ICI-ICI (nivolumab + ipilimumab) whereas 502 (42.8%) an ICI-TKI combination, mainly avelumab + axitinib (27.1%) and pembrolizumab + lenvatinib (14.3%). Overall, median overall survival (mOS) was 36.2 months (95% CI 31.1 – 38.5) with a median follow up of 15.5 months. The c-index of Meet-URO resulted higher than IMDC score (0.68 vs 0.65). In particular, the mOS resulted more distinctive within the Meet-URO prognostic groups: 45.8 months for group 1 (12.9% of patients), 55.0 for group 2 (25.7%), 38.1 for group 3 (23.5%), 20.9 months for group 4 (29.6%) and 10.4 for group 5 (8.2%). On the other hand, mOS was 45.8 months for IMDC favorable-risk (19.5% of patients), 38.2 for intermediate-risk (53.7%) and 16.2 for poor-risk (26.8%). Conclusions: In this large-scale real-world external validation analysis on mRCC patients receiving first-line immune-combinations, Meet-URO confirmed higher prognostic accuracy compared to IMDC. A further validation is planned in the ongoing Italian prospective Meet-URO 33 (REGAL) study (PMID: 38914928).
External validation of the novel prognostic Meet-URO score in Metastatic Renal Cell Carcinoma on First Line Immune-combination therapy. - Proceedings from the Second International Urology Cancer Summit, 27th September, Portsmouth, UK / Ghose, Aruni; Signori, Alessio; Brown, Nicholas; Haywood, Sophia; Tapia, Jose; Vijay, Anupama; Cheung, Michael; Mahajan, Ishika; Fiala, Ondrej; Abrol, Ritika; Chauhan, Vishwani; Shwe Yee Soe, Yamin; Zargham, Anum; Ashley, Sophie; Smith, Michelle; Hardy, Orla; Johnston, Emma; Sarwer, Abdullah; Kyaw Tun, Kyaw; Challapalli, Amarnath; Shrestha, Roshani; Ürün, Yüksel; Meegan, James; Rescigno, Pasquale; Parkes, Joanne; Smalley, Benjamin; Anpalakhan, Shobana; Buono, Francesco; Poprach, Alexandr; Yuen Chun Teoh, Jeremy; Murianni, Veronica; Catalano, Fabio; Bimbatti, Davide; Buti, Sebastiano; Fornarini, Giuseppe; Banna, Giuseppe; Elena Rebuzzi, Sara. - In: THERAPEUTIC ADVANCES IN UROLOGY. - ISSN 1756-2872. - 16:(2024), pp. IUCS20761-50 – Merit Award.13-IUCS20761-50 – Merit Award.14. [10.1177/17562872241277067]
External validation of the novel prognostic Meet-URO score in Metastatic Renal Cell Carcinoma on First Line Immune-combination therapy. - Proceedings from the Second International Urology Cancer Summit, 27th September, Portsmouth, UK
Sebastiano ButiInvestigation
;
2024-01-01
Abstract
Objective: First-line immune-combination therapy based on immune checkpoint inhibitors (ICIs) and tyrosine kinase inhibitors (TKIs) are the new mainstay in metastatic renal cell cancer (mRCC). In this setting, there is a dearth of standard prognostic/predictive parameters to guide treatment choice. The novel prognostic Meet-URO score (IMDC score + bone metastases and neutrophil-to-lymphocyte ratio - NLR) showed a higher prognostic accuracy than IMDC in 306 patients on first-line nivolumab + ipilimumab in the Italian Expanded Access Program (PMID: 36493602). Hence, the necessity to externally validate and expand to other first-line immune-combination settings. Methods: Twenty-seven European centres were included. Baseline patient and tumour characteristics were collected, including the IMDC score along with the presence of pre-treatment bone metastases, neutrophils, and lymphocytes for calculating the Meet-URO score. The prognostic performance of Meet-URO and IMDC scores were compared and defined by the Harrell’s c-index. Results: 1174 mRCC patient data was retrospectively collected. The median age was 64. 72.8% were male, 54.2% received nephrectomy, 62% were metastatic at diagnosis and 86.7% had clear-cell histology. 35% had bone metastases and 51.6% had NLR ⩾ 3.2. 672 (57.2%) patients received ICI-ICI (nivolumab + ipilimumab) whereas 502 (42.8%) an ICI-TKI combination, mainly avelumab + axitinib (27.1%) and pembrolizumab + lenvatinib (14.3%). Overall, median overall survival (mOS) was 36.2 months (95% CI 31.1 – 38.5) with a median follow up of 15.5 months. The c-index of Meet-URO resulted higher than IMDC score (0.68 vs 0.65). In particular, the mOS resulted more distinctive within the Meet-URO prognostic groups: 45.8 months for group 1 (12.9% of patients), 55.0 for group 2 (25.7%), 38.1 for group 3 (23.5%), 20.9 months for group 4 (29.6%) and 10.4 for group 5 (8.2%). On the other hand, mOS was 45.8 months for IMDC favorable-risk (19.5% of patients), 38.2 for intermediate-risk (53.7%) and 16.2 for poor-risk (26.8%). Conclusions: In this large-scale real-world external validation analysis on mRCC patients receiving first-line immune-combinations, Meet-URO confirmed higher prognostic accuracy compared to IMDC. A further validation is planned in the ongoing Italian prospective Meet-URO 33 (REGAL) study (PMID: 38914928).I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
