The impact of body composition parameters on severe toxicity of nivolumab

Hirsch, Laure; Bellesœur, Audrey; Boudou‐Rouquette, Pascaline; Arrondeau, Jennifer; Thomas-Schoemann, Audrey; Kirchgesner, Julien; Gervais, Claire; Jouinot, Anne; Chapron, Jeanne; Giraud, Frédérique; Wislez, Marie; Alexandre, Jérôme; Blanchet, Benoı̂t; Goldwasser, François

doi:10.1016/j.ejca.2019.11.003

Cited by 35 publications

(29 citation statements)

References 40 publications

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“… 7 In addition, an increasing number of studies are focusing on the impact of sarcopenia on ICI treatment efficacy. 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 However, most previous studies on the topic had a retrospective design and included a small number of patients in whom various methods were employed for the diagnosis of sarcopenia. Therefore, the predictive value of sarcopenia in ICI therapy requires elucidation.…”

Section: Introductionmentioning

confidence: 99%

Predictive impact of sarcopenia in solid cancers treated with immune checkpoint inhibitors: a meta‐analysis

Takenaka

Oya

Takemoto

et al. 2021

J cachexia sarcopenia muscle

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Sarcopenia, which is characterized by a decrease in muscle quantity or quality, is commonly observed in patients with cancer. Recent research has reported contradictory results on the association between sarcopenia and the efficacy of immune checkpoint inhibitors (ICIs). We conducted a systematic review and meta-analysis to investigate this discrepancy. We systematically searched three electronic databases to identify articles reporting on the association between sarcopenia and treatment outcomes in patients with solid cancers who received ICIs. The outcomes assessed were hazard ratios (HRs) for overall survival (OS) and progression-free survival (PFS), and odds ratios (ORs) for objective response rate (ORR), disease control rate (DCR), and toxicity. Pooled estimates and their 95% confidence intervals (CIs) were calculated. A total of 2501 patients from 26 studies were analysed. Sarcopenia was observed in 44.7% (95% CI: 38.2-51.3) of the patients and was significantly associated with poor survival (HR = 1.55, 95% CI = 1.32-1.82 for OS and HR = 1.61, 95% CI = 1.35 to 1.93 for PFS). The HRs (95% CIs) for OS according to the diagnostic measures used were 1.97 (0.88-4.41) for psoas muscle index (PMI), 1.41 (0.87-2.28) for skeletal muscle density (SMD), and 1.43 (1.23-1.67) for skeletal mass index (SMI). The HRs (95% CIs) for PFS were 1.86 (1.08-3.21) for PMI, 1.27 (0.94-1.71) for SMD, and 1.38 (1.11-1.71) for SMI. Poor radiological response to ICI therapy was observed in patients with sarcopenia (OR = 0.52, 95% CI = 0.34-0.80 for ORR and OR = 0.45, 95% CI = 0.30-0.67 for DCR). The ORs for ORR (95% CIs) were 0.56 (0.15-2.05) for PMI and 0.78 (0.56-1.09) for SMI. The oncologic outcomes associated with melanoma and non-small cell lung cancer (NSCLC) were comparable with those observed overall (HR for OS = 2.02, 95% CI = 1.26-3.24 for melanoma and HR for OS = 1.61, 95% CI = 1.19-2.18 for NSCLC). In contrast, the occurrence of severe toxicity was not associated with sarcopenia (OR = 1.13, 95% CI = 0.51-2.52). Poor survival and poor response in patients with sarcopenia indicate a negative association between sarcopenia and efficacy of ICIs. Sarcopenia's predictive ability is consistent across various tumour types. For the selection of patients who may respond to ICIs pre-therapeutically, the presence of sarcopenia should be assessed in clinical practice.

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Section: Introductionmentioning

confidence: 99%

Predictive impact of sarcopenia in solid cancers treated with immune checkpoint inhibitors: a meta‐analysis

Takenaka

Oya

Takemoto

et al. 2021

J cachexia sarcopenia muscle

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“…Moreover, sarcopenia developing during treatment versus no changes related to skeletal muscle mass during treatment also affected patient survival. Only a few studies have reported the effect of sarcopenia on irAEs, which showed that sarcopenia increased their incidence (49,50). However, a meta-analysis reported that sarcopenia had no relation with irAEs (19).…”

Section: Discussionmentioning

confidence: 99%

Prognostic Impact of Sarcopenia on Clinical Outcomes in Malignancies Treated With Immune Checkpoint Inhibitors: A Systematic Review and Meta-Analysis

Wang

Tong

et al. 2021

Front. Oncol.

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BackgroundThe effect of sarcopenia on the clinical outcomes of patients with malignant neoplasms receiving immune checkpoint inhibitors (ICIs) is unclear. The aim of this study was to evaluate the effect and survival of patients with malignancies and sarcopenia receiving ICIs.MethodsWe systematically searched related studies in PubMed, Embase, and Cochrane Library up to March 2021 according to the inclusion and exclusion criteria. Information pertaining to the hazard ratio (HR) corresponding to 95% confidence interval (CI) of overall survival (OS) and progression-free survival (PFS) as determined by univariate and multivariate analyses; the odds ratio (OR) corresponding to the 95% CI of the disease control rate (DCR) and objective response rate (ORR); and immune-related adverse events (irAEs) was collected and analyzed using the RevMan 5.4 software. Study heterogeneity and sensitivity were also assessed.ResultsA total of 19 studies were finalized that included 1763patients with lung, gastrointestinal, and head and neck cancers as well as those with melanoma, renal cell carcinoma, urothelial carcinoma, pancreatic cancer, and soft tissue sarcoma. According to univariate and multivariate analyses, patients with sarcopenia at pre-immunotherapy had poorer PFS and OS than those without. HRs and the corresponding 95% CI of PFS were 1.91(1.55–2.34, p <0.00001) and 1.46 (1.20–1.78, p =0.0001), respectively, and HRs and the corresponding 95% CI of OS were 1.78 (1.47–2.14, p <0.00001) and 1.73 (1.36–2.19, p <0.0001), respectively. Patients with sarcopenia showed poor PFS and OS during treatment. In addition, patients with sarcopenia had worse ORR (OR 0.46, 95% CI 0.28–0.74, p = 0.001) and DCR (OR 0.44, 95% CI 0.31–0.64, p<0.0001); however, the incidence of irAEs of any grade and high-grade in patients with sarcopenia did not increase, OR and the corresponding 95% CI were 0.58(0.30–1.12, p = 0.10) and 0.46(0.19–1.09, p = 0.08). Further, we performed subgroup analysis, skeletal muscle mass index (SMI) and psoas muscle mass index (PMI) stratification. In the SMI group, patients with sarcopenia had poor ORR, DCR, PFS, and OS than those without. In the PMI group, sarcopenia had poor ORR,DCR, and was a poor prognostic factor for PFS and OS according to univariate analysis but had no effect on PFS and OS according to multivariate analysis.ConclusionsPatients with malignancies and sarcopenia at pre-immunotherapy or follow-up visits had poorer clinical outcomes than those without, and sarcopenia was a poor predictive factor of ICI immunotherapy outcomes.

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“…Obesity has also been associated with higher rates of autoimmune and inflammatory diseases in the general population [ 37 ], but studies on patients treated with immunotherapies have yielded discrepant results. Some showed that BMI had no predictive value for the incidence of irAEs [ 12 , 16 , 22 , 38 ], whereas others reported a significant increase in the risk of irAEs with increasing BMI [ 15 , 39 , 40 , 41 , 42 , 43 , 44 ]. The exact mechanism of this association is not completely understood.…”

Section: Discussionmentioning

confidence: 99%

“…Biomarkers of metabolic syndrome are also being investigated [ 61 ] and may also be useful for improving the characterization of body composition and outcome on anticancer treatments, including immunotherapy. Furthermore, the percent lean tissue is often low in obese patients [ 64 ], potentially affecting pharmacokinetics and exposure to treatment [ 38 , 65 ]. An association between sarcopenic obesity, defined as obesity with severe muscle depletion and survival outcome, has been clearly described for chemotherapy [ 66 , 67 , 68 ] but has rarely been reported for immunotherapy [ 44 ].…”

Section: Discussionmentioning

confidence: 99%

Association between Body Mass Index and Survival Outcome in Metastatic Cancer Patients Treated by Immunotherapy: Analysis of a French Retrospective Cohort

Collet

Delrieu

Bouhamama

et al. 2021

Cancers

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The response to immunotherapy has been little investigated in overweight and obese cancer patients. We evaluated the relationships between BMI, toxicity, and survival in patients treated by immunotherapy for metastatic cancer. We included metastatic cancer patients treated by immunotherapy between January 2017 and June 2020 at the Centre Léon Bérard. In total, 272 patients were included: 64% men and 36% women, with a median age of 61.4 years. BMI ≥ 25 in 34.2% and 50% had non-small cell lung cancer (n = 136). Most received monotherapy, with nivolumab in 41.9% and pembrolizumab in 37.9%. Toxicity, mostly dysthyroiditis, occurred in 41%. Median overall survival (OS), estimated by Kaplan–Meier analysis, was significantly longer for patients with a BMI ≥ 25 than for those with a BMI < 25 (24.8 versus 13.7 months HR = 0.63; 95% CI 0.44–0.92, p = 0.015), and for patients experiencing toxicity than for those without toxicity (NR versus 7.8 months, HR = 0.22; 95% CI 0.15–0.33, p < 0.001). Adjusted OS was associated with toxicity, and the occurrence of toxicity was associated with sex and histological features but not with BMI. Thus, being overweight and experiencing toxicity was associated with longer overall survival in patients treated by immunotherapy. More attention should be paid to body composition in the care of cancer patients.

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The impact of body composition parameters on severe toxicity of nivolumab

Cited by 35 publications

References 40 publications

Predictive impact of sarcopenia in solid cancers treated with immune checkpoint inhibitors: a meta‐analysis

Predictive impact of sarcopenia in solid cancers treated with immune checkpoint inhibitors: a meta‐analysis

Prognostic Impact of Sarcopenia on Clinical Outcomes in Malignancies Treated With Immune Checkpoint Inhibitors: A Systematic Review and Meta-Analysis

Association between Body Mass Index and Survival Outcome in Metastatic Cancer Patients Treated by Immunotherapy: Analysis of a French Retrospective Cohort

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