Dataset Information

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

ABSTRACT:

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.

SUBMITTER: Rebuzzi SE

PROVIDER: S-EPMC9524042 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature

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Publications

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

Rebuzzi Sara Elena SE Signori Alessio A Banna Giuseppe Luigi GL Gandini Annalice A Fornarini Giuseppe G Damassi Alessandra A Maruzzo Marco M De Giorgi Ugo U Basso Umberto U Chiellino Silvia S Galli Luca L Zucali Paolo Andrea PA Fantinel Emanuela E Naglieri Emanuele E Procopio Giuseppe G Milella Michele M Boccardo Francesco F Fratino Lucia L Pipitone Stefania S Ricotta Riccardo R Panni Stefano S Mollica Veronica V Sorarù Mariella M Santoni Matteo M Cortellini Alessio A Prati Veronica V Soto Parra Hector Josè HJ Santini Daniele D Atzori Francesco F Di Napoli Marilena M Caffo Orazio O Messina Marco M Morelli Franco F Prati Giuseppe G Nolè Franco F Vignani Francesca F Cavo Alessia A Roviello Giandomenico G Rescigno Pasquale P Buti Sebastiano S

Journal of translational medicine 20220930 1

<h4>Background</h4>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.<h4>Methods</h4>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 (receive ...[more]

PMID: 36180954

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Project description:BackgroundThe prognostic value of the Geriatric 8 (G8) screening score in metastatic renal cell carcinoma (mRCC) patients receiving first-line immunotherapy remains unclear. This study aimed to evaluate the prognostic role of G8 within the context of the Meet-URO classification in mRCC patients treated with first-line ipilimumab-nivolumab.MethodsThis retrospective multicentre study analysed 106 mRCC patients treated with first-line ipilimumab-nivolumab. G8 and Meet-URO scores were calculated before treatment initiation. Primary endpoint was overall survival (OS), defined as duration from first administration of Nivolumab to death. OS was analysed in relation to age groups, G8 scores, and Meet-URO score categories, with data censored for patients still alive at the last follow-up. The secondary endpoint, progression-free survival (PFS), was measured from initiating Nivolumab to the earliest instance of disease progression or death. OS and PFS were assessed using Kaplan-Meier methods and Cox regression analyses. The reporting of this study conforms to the REMARK guidelines.ResultsPatients with G8 > 14 had more favorable IMDC and Meet-URO risk classifications and lower neutrophil-to-lymphocyte ratios. While PFS did not differ significantly between G8 ≤ 14 and >14 groups (1-year 29.3% vs 46.2%, p = 0.2), OS was significantly longer in G8 > 14 group (1-year 76.1% vs 58.6%, p = 0.006). In multivariable analysis, G8 ≤ 14 was independently associated with worse OS (HR 2.36, 95% CI 1.06-5.08, p = 0.03) but not PFS. The Meet-URO score was prognostic for both PFS and OS. In patients ≥70 years, G8 lost its prognostic value, while Meet-URO remained prognostic for OS.ConclusionsThe G8 score is an independent prognostic factor for OS but not PFS in mRCC patients receiving first-line ipilimumab-nivolumab. The Meet-URO score shows consistent prognostic ability for PFS and OS across age groups. These findings suggest that while G8 may be useful for individual patient-level OS prediction, the Meet-URO score may be superior for guiding treatment decisions in clinical practice.

Project description:BackgroundImmune checkpoint inhibitors (ICIs) are currently the standard of care for metastatic urothelial cancer (mUC) after the failure of previous platinum-based chemotherapy. The choice of further therapy after ICI progression is a new challenge, and scarce data support it. We aimed to examine the outcomes of mUC patients after progression to ICI, especially when receiving chemotherapy.MethodsData were retrospectively collected from clinical records of mUC patients whose disease progressed to anti-programmed death 1 (PD-1)or programmed death ligand 1 (PD-L1) therapy at 14 Italian centers. Patients were grouped according to ICI therapy setting into SALVAGE (ie, ICI delivered ⩾ second-line therapy after platinum-based chemotherapy) and NAÏVE (ie, first-line therapy) groups. Progression-free survival (PFS) and overall survival (OS) rates were calculated using the Kaplan-Meier method and compared among subgroups. Cox regression assessed the effect of treatments after progression to ICI on OS. Objective response rate (ORR) was calculated as the sum of partial and complete radiologic responses.ResultsThe study population consisted of 201 mUC patients who progressed after ICI: 59 in the NAÏVE cohort and 142 in the SALVAGE cohort. Overall, 52 patients received chemotherapy after ICI progression (25.9%), 20 (9.9%) received ICI beyond progression, 115 (57.2%) received best supportive care only, and 14 (7.0%) received investigational drugs. Objective response rate to chemotherapy in the post-ICI setting was 23.1% (28.0% in the NAÏVE group and 18.5% in the SALVAGE group). Median PFS and OS to chemotherapy after ICI-PD was 5 months (95% confidence interval [CI]: 3-11) and 13 months (95% CI: 7-NA) for the NAÏVE group; 3 months (95% CI: 2-NA) and 9 months (95% CI: 6-NA) for the SALVAGE group, respectively. Overall survival from ICI initiation was 17 months for patients receiving chemotherapy (hazard ratio [HR] = 0.09, p < 0.001), versus 8 months for patients receiving ICI beyond progression (HR = 0.13, p < 0.001), and 2 months for patients who did not receive further active treatment (p < 0.001).ConclusionsChemotherapy administered after ICI progression for mUC patients is advisable irrespective of the treatment line.

Project description:BackgroundDespite the survival advantage, not all metastatic renal cell carcinoma (mRCC) patients achieve a long-term benefit from immunotherapy. Moreover, the identification of prognostic biomarkers is still an unmet clinical need.MethodsThis multicenter retrospective study investigated the prognostic role of peripheral-blood inflammatory indices and clinical factors to develop a novel prognostic score in mRCC patients receiving at least second-line nivolumab. The complete blood count before the first cycle of therapy was assessed by calculating neutrophil-to-lymphocyte ratio (NLR), derived NLR (dNLR), lymphocyte-to-monocyte ratio (LMR), platelet-to-lymphocyte ratio (PLR), systemic inflammation index (SII), and systemic inflammation response index (SIRI). Clinical factors included pre-treatment International Metastatic RCC Database Consortium (IMDC) score, line of therapy, and metastatic sites.ResultsFrom October 2015 to November 2019, 571 mRCC patients received nivolumab as second- and further-line treatment in 69% and 31% of cases. In univariable and multivariable analyses all inflammatory indices, IMDC score, and bone metastases significantly correlated with overall survival (OS). The multivariable model with NLR, IMDC score, and bone metastases had the highest c-index (0.697) and was chosen for the developing of the score (Schneeweiss scoring system). After internal validation (bootstrap re-sampling), the final index (Meet-URO score) composed by NLR, IMDC score, and bone metastases had a c-index of 0.691. It identified five categories with distinctive OSs: group 1 (median OS - mOS = not reached), group 2 (mOS = 43.9 months), group 3 (mOS = 22.4 months), group 4 (mOS = 10.3 months), and group 5 (mOS = 3.2 months). Moreover, the Meet-URO score allowed for a fine risk-stratification across all three IMDC groups.ConclusionThe Meet-URO score allowed for the accurate stratification of pretreated mRCC patients receiving nivolumab and is easily applicable for clinical practice at no additional cost. Future steps include its external validation, the assessment of its predictivity, and its application to first-line combinations.

Dataset Information

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

Methods

Results

Conclusions

Publications

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

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