Prognostic and predictive molecular biomarkers in metastatic renal cell carcinoma patients treated with immune checkpoint inhibitors: a systematic review

Rebuzzi, Sara Elena; Perrone, Fabiana; Bersanelli, Melissa; Bregni, Giacomo; Milella, Michèle; Buti, Sebastiano

doi:10.1080/14737159.2019.1680286

Cited by 22 publications

(26 citation statements)

References 61 publications

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“… 5 , 6 It should be noted that mRCC is often associated with a highly-variable clinical course, spanning from indolent to rapidly-progressing disease, 7 as a reflection of its well-known heterogeneity. 9 …”

Section: Introductionmentioning

confidence: 99%

“…molecular and genomic signatures) are under investigation, no validated biomarker has yet to reach everyday clinical practice. 9 …”

Section: Introductionmentioning

confidence: 99%

“…9 As a result, the identification of biomarkers to select patients most and least likely to benefit from immunotherapy is a clinically unmet need and a critical issue of clinical research. 9 Although new potential biomarkers (e.g. molecular and genomic signatures) are under investigation, no validated biomarker has yet to reach everyday clinical practice.…”

Section: Introductionmentioning

confidence: 99%

“…molecular and genomic signatures) are under investigation, no validated biomarker has yet to reach everyday clinical practice. 9 Cancer-associated inflammation has been associated with worse outcomes and lower therapeutic responses in cancer patients across different tumor types. 10,11 Easily-achievable peripheral blood parameters, reflecting an inflamed state, have been investigated as potential biomarkers in different tumors (including RCC), settings, and therapies.…”

Section: Introductionmentioning

confidence: 99%

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Inflammatory indices and clinical factors in metastatic renal cell carcinoma patients treated with nivolumab: the development of a novel prognostic score (Meet-URO 15 study)

et al. 2021

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Background: Despite 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. Methods: This 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. Results: From 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. Conclusion: The 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.

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Section: Introductionmentioning

confidence: 99%

“…molecular and genomic signatures) are under investigation, no validated biomarker has yet to reach everyday clinical practice. 9 …”

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Inflammatory indices and clinical factors in metastatic renal cell carcinoma patients treated with nivolumab: the development of a novel prognostic score (Meet-URO 15 study)

et al. 2021

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“…Toward this end, there are many trials of combinations that either do not increase the response rate or, if they do, at greatly increased toxicity [7]. This is particularly true in melanoma when combining checkpoint inhibitors, however, combination with chemotherapy [8] and tyrosine kinase inhibitors [9] in lung cancers and renal cancer, respectively, have benefit in progression free survival and overall survival with reportedly acceptable toxicity.…”

Section: Practical Issuesmentioning

confidence: 99%

Why do the majority of patients not respond at all, or only partially or transiently, to immunotherapy?

Dalgleish

2019

Expert Review of Anticancer Therapy

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

Catalano,

Rebuzzi,

Maruzzo

et al. 2023

JAMA Netw Open

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ImportanceLow sodium levels have been associated with negative outcomes among patients with metastatic renal cell carcinoma (mRCC) receiving therapies other than immune checkpoint inhibitors (ICIs).ObjectiveTo investigate the role of natremia in patients with mRCC receiving nivolumab as a second-line or subsequent therapy.Design, Setting, and ParticipantsIn 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.ExposureNivolumab 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 (&lt;140 or ≥140 mEq/L).Main Outcomes and MeasuresThe 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.ResultsA 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 RelevanceIn 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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Prognostic and predictive molecular biomarkers in metastatic renal cell carcinoma patients treated with immune checkpoint inhibitors: a systematic review

Cited by 22 publications

References 61 publications

Inflammatory indices and clinical factors in metastatic renal cell carcinoma patients treated with nivolumab: the development of a novel prognostic score (Meet-URO 15 study)

Inflammatory indices and clinical factors in metastatic renal cell carcinoma patients treated with nivolumab: the development of a novel prognostic score (Meet-URO 15 study)

Why do the majority of patients not respond at all, or only partially or transiently, to immunotherapy?

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

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