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Multicenter Study
. 2023 Nov 1;6(11):e2345185.
doi: 10.1001/jamanetworkopen.2023.45185.

Sodium Levels and Outcomes in Patients With Metastatic Renal Cell Carcinoma Receiving Nivolumab

Martina Catalano  1 , Sara Elena Rebuzzi  2   3 , Marco Maruzzo  4 , Ugo De Giorgi  5 , Sebastiano Buti  6   7 , Luca Galli  8 , Giuseppe Fornarini  9 , Paolo Andrea Zucali  10   11 , Giuseppe Procopio  12 , Silvia Chiellino  13 , Michele Milella  14 , Fabio Catalano  9 , Stefania Pipitone  15 , Riccardo Ricotta  16 , Mariella Sorarù  17 , Veronica Mollica  18 , Marianna Tudini  19 , Lucia Fratino  20 , Veronica Prati  21 , Orazio Caffo  22 , Francesco Atzori  23 , Franco Morelli  24 , Giuseppe Prati  25 , Franco Nolè  26 , Francesca Vignani  27 , Alessia Cavo  28 , Marilena Di Napoli  29 , Andrea Malgeri  30 , Emanuele Naglieri  31 , Alessio Signori  32 , Giuseppe Luigi Banna  33   34 , Pasquale Rescigno  35 , Lorenzo Antonuzzo  36 , Giandomenico Roviello  1
Affiliations
Multicenter Study

Sodium Levels and Outcomes in Patients With Metastatic Renal Cell Carcinoma Receiving Nivolumab

Martina Catalano et al. JAMA Netw Open. .

Abstract

Importance: Low sodium levels have been associated with negative outcomes among patients with metastatic renal cell carcinoma (mRCC) receiving therapies other than immune checkpoint inhibitors (ICIs).

Objective: To investigate the role of natremia in patients with mRCC receiving nivolumab as a second-line or subsequent therapy.

Design, setting, and participants: In this retrospective cohort study, the clinical and biochemical data of patients with mRCC receiving nivolumab were collected from October 2015 to November 2019 as part of a multicenter Italian study. Data analysis was performed from February to March 2023.

Exposure: Nivolumab was administered intravenously at a dose of 3 mg/kg every 2 weeks and, since May 2018, at a fixed dose of 240 mg every 2 weeks or 480 mg every 4 weeks. Patients were divided into 2 groups according to their median serum sodium value (<140 or ≥140 mEq/L).

Main outcomes and measures: The primary outcomes were the associations of pre-ICI and post-ICI sodium levels with overall survival (OS), progression-free survival (PFS), objective response rate, and disease control rate (DCR). The Kaplan-Meier method was used to estimate PFS and OS, and differences between groups were compared using the log-rank test.

Results: A total of 401 patients with mRCC receiving nivolumab as second-line therapy were evaluated, and 355 eligible patients (median [range] age, 76 [44-84] years; 258 male patients [72.7%]) were included in the final cohort. Among patients with pre-ICI sodium greater than or equal to 140 mEq/L compared with those with sodium less than 140 mEq/L, the median PFS was 9.3 months (95% CI, 6.5-11.5 months) vs 7.4 months (95% CI, 4.6-10.1 months; P = .90), and the median OS was 29.2 months (95% CI, 21.8-35.9 months) vs 20.0 months (95% CI, 14.1-26.8 months; P = .03). Patients with post-ICI sodium values greater than or equal to 140 mEq/L had longer PFS (11.1 months [95% CI, 8.5-1.5 months] vs 5.1 months [95% CI, 4.1-7.5 months]; P = .01) and OS (32.9 months [95% CI, 25.1-42.6 months] vs 17.1 months [95% CI, 12.6-24.5 months]; P = .006) compared with patients with sodium values less than 140 mEq/L. Patients with both pre-ICI and post-ICI sodium values greater than or equal to 140 mEq/L exhibited a significant improvement in clinical outcomes compared with those with a value less than 140 mEq/L (PFS, 11.5 months [95% CI, 8.8-16.4 months] vs 5.8 months [95% CI, 4.4-8.3 months]; P = .008); OS, 37.6 months [95% CI, 29.0-49.9 months] vs 19.4 months [95% CI, 14.1-24.5 months]; P = .01). Moreover, sodium levels greater than or equal to 140 mEq/L were associated with significantly better DCR than lower sodium levels.

Conclusions and relevance: In this retrospective cohort study of patients with mRCC receiving nivolumab, sodium values greater than or equal to 140 mEq/L, both before and/or after ICI, were associated with better OS and PFS, as well as a higher DCR, compared with levels less than 140 mEq/L. These findings suggest that sodium levels may be associated with survival outcomes in patients with mRCC and may have potential use as variables to consider in patients' risk scores.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Rebuzzi reported receiving personal fees from Bristol-Myers Squibb, Astellas, GlaxoSmithKline, Janssen, and Merck Sharp & Dohme outside the submitted work. Dr Zucali reported receiving personal fees from Pfizer, Astellas, Janssen, Merck Sharp & Dohme, Bristol-Myers Squibb, Novartis, Ipsen, Merck, AstraZeneca, and Bayer outside the submitted work. Dr Procopio reported receiving personal fees from AstraZeneca, Bayer, Merck, Roche, Pfizer, Bristol Myers Squibb, MSD: Medical & Commercial Oncology Careers, and Eisai; and grants from Ipsen and Janssen outside the submitted work. Dr Chiellino reported receiving personal fees from Bristol-Myers Squibb, Ipsen, Pierre Fabre, Bayer, Merck Sharp & Dohme, and Novartis outside the submitted work. Dr Pipitone reported receiving grants from Merck Sharp & Dohme, Ipsen, Eisai, Pfizer, Bristol-Myers Squibb, and Pharmamar; and nonfinancial support (provision of access to data, information, and educational resources) from Jannsen and Merck outside the submitted work. Dr Caffo reported receiving personal fees from Advanced Accelerator Applications, Astellas, AstraZeneca, Bayer, Janssen, Ipsen, Merck Sharp & Dohme, Pfizer, and Recordati outside the submitted work. Dr Morelli reported receiving personal fees from Pfizer and Merck Sharp & Dohme outside the submitted work. Dr Banna reported receiving personal fees from Astellas and AstraZeneca outside the submitted work. Dr Rescigno reported receiving personal fees from AstraZeneca, Janssen, Ipsen, Pfizer, and Merck Sharp & Dohme outside the submitted work. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Kaplan-Meier Survival Estimate According to Serum Sodium Values
Graphs show progression-free survival (PFS) by pre–immune checkpoint inhibitor (ICI) sodium values (A), PFS by post-ICI sodium values (B), overall survival (OS) by pre-ICI sodium values (C), and OS by post-ICI sodium values (D). To convert sodium to millimoles per liter, multiply by 1.
Figure 2.
Figure 2.. Kaplan-Meier Survival Estimate According to Serum Sodium Values Both Before and After Immune Checkpoint Inhibitor Therapy
Graphs show progression-free survival (PFS) (A) and overall survival (OS) (B). To convert sodium to millimoles per liter, multiply by 1.
See this image and copyright information in PMC

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