International multicenter real-world REGistry for patients with metastatic renAL cell carcinoma - Meet-URO 33 study (REGAL study).

BACKGROUND: Nowadays, different therapeutic options are available for the first-line treatment of metastatic renal cell carcinoma (mRCC). Immuno-combinations are the standard first-line therapy in all mRCC patients regardless of the International Metastatic RCC Database Consortium (IMDC) risk category, even though TKI monotherapy is still a therapeutic option in selected patients. However, comparisons between the different first-line treatment strategies are lacking and few real-world data are available in this setting. For this reason, the regimen choice represents an important issue in clinical practice and the optimal treatment sequence remains unclear. METHODS: The REGAL study is a multicentric prospective observational study enrolling mRCC patients treated with first-line systemic therapy according to clinical practice in a real-world setting. A retrospective cohort of mRCC patients who received first-line systemic therapy from the 1st of January 2021 will also be included. The primary objective is to identify potential prognostic and predictive factors that could help guide the treatment choice; secondary objectives included the assessment of the prognostic performance of the novel prognostic Meet-URO score (IMDC score + neutrophil-to-lymphocyte ratio + bone metastases) compared with the IMDC score and the comparison between treatment strategies according to response and survival outcomes and toxicity profile. DISCUSSION: Considering the high number of therapeutic first-line strategies available for mRCC, the identification of clinical prognostic and predictive factors to candidate patients to a preferable systemic therapy is still an unmet clinical need. The Meet-URO 33 study aims to provide a large-scale real-world database on mRCC patients, to identify the clinical predictive and prognostic factors and the different performances between the ICI-based combinations according to response, survival and toxicity. TRIAL REGISTRATION: CESC IOV 2023-78.

The prognostic value of the previous nephrectomy in pretreated metastatic renal cell carcinoma receiving immunotherapy: a sub-analysis of the Meet-URO 15 study.

BACKGROUND: Nephrectomy is considered the backbone of managing patients with localized and selected metastatic renal cell carcinoma (mRCC). The prognostic role of nephrectomy has been widely investigated with cytokines and targeted therapy, but it is still unclear in the immunotherapy era. METHODS: We investigated the Meet-URO-15 study dataset of 571 pretreated mRCC patients receiving nivolumab as second or further lines about the prognostic role of the previous nephrectomy (received in either the localized or metastatic setting) in the overall population and according to the Meet-URO score groups. RESULTS: Patients who underwent nephrectomy showed a significantly reduced risk of death (HR 0.44, 95% CI 0.32-0.60, p < 0.001) with a longer median overall survival (OS) (35.9 months vs 12.1 months), 1-year OS of 71.6% vs 50.5% and 2-years OS of 56.5% vs 22.0% compared to those who did not. No significant interaction between nephrectomy and the overall five Meet-URO score risk groups was observed (p = 0.17). It was statistically significant when merging group 1 with 2 and 3 and group 4 with 5 (p = 0.038) and associated with a longer OS for the first three prognostic groups (p < 0.001), but not for groups 4 and 5 (p = 0.54). CONCLUSIONS: Our study suggests an overall positive impact of the previous nephrectomy on the outcome of pretreated mRCC patients receiving immunotherapy. The clinical relevance of cytoreductive nephrectomy, optimal timing and patient selection deserves further investigation, especially for patients with Meet-URO scores of 1 to 3, who are the once deriving benefit in our analyses. However, that benefit is not evident for IMDC poor-risk patients (including the Meet-URO score groups 4 and 5) and a subgroup of IMDC intermediate-risk patients defined as group 4 by the Meet-URO score.

Treatment patterns, outcomes and clinical characteristics in advanced renal cell carcinoma: a real-world US study.

Aim: Assessing treatment patterns, outcomes and clinical characteristics in advanced renal cell carcinoma clinical practice. Materials & methods: A US cross-sectional physician survey conducted February-September 2019. Results: Surveyed physicians reported first-line treatment of 445 patients involving tyrosine kinase inhibitor monotherapy (51.0%), immuno-oncology (IO/IO combination) therapy (25.8%) or other regimens (23.1%). A total of 60.9% had physician-assessed IMDC risk. Of these 61.9, 50.9 and 27.6% of patients with favorable, intermediate and poor risk, respectively, received tyrosine kinase inhibitor monotherapy. A total of 16.7, 26.9 and 34.5% of patients with favorable, intermediate or poor risk received IO/IO combination therapy. Complete/partial responses (∼35% patients) remained comparable across first-line treatments. Conclusion: Guideline-recommended therapies are not widely prescribed. Many patients experienced poor clinical outcomes highlighting a need for more effective treatments.

Biomarkers to predict prognosis and response to checkpoint inhibitors.

Nivolumab is a fully human immunoglobulin (Ig) G4 antibody that selectively inhibits the programmed death 1 (PD-1) immune checkpoint molecule, and has recently been launched for the treatment of renal cell cancer (RCC) in Japan. Based on its promising anti-tumor efficacy and manageable safety profile demonstrated in the phase III Checkmate 025 trial, nivolumab therapy is rapidly being introduced in metastatic RCC clinical practice. The phase Ia study of atezolizumab, which is a humanized anti-PD-ligand 1 (PD-L1) monoclonal IgG1 antibody, also demonstrated excellent treatment results. The identification of biomarkers to predict the response and side-effects of checkpoint inhibitor therapy is thus urgently needed. In this review, we introduce the current candidate biomarkers of immune checkpoint inhibitor therapy. Based on the mechanism of efficacy, the number of neoantigens and expression of major histocompatibility complex molecules are strong candidate biomarkers. Despite the various interference factors, PD-L1 expression can be considered a potential biomarker. In terms of clinical factors, serum clinical factors and severity of adverse events are examined. Although further implementation in prospective studies is necessary, if validated, these biomarkers can be utilized to measure therapeutic response and design treatment strategies for metastatic RCC.