Predictive value of skeletal muscle mass for immunotherapy with nivolumab in non‐small cell lung cancer patients: A “hypothesis‐generator” preliminary report

Cortellini, Alessio; Verna, Lucilla; Porzio, Giampiero; Bozzetti, Federico; Palumbo, Pierpaolo; Masciocchi, Carlo; Cannita, Katia; Parisi, Alessandro; Brocco, Davide; Tinari, Nicola; Ficorella, Corrado

doi:10.1111/1759-7714.12965

Cited by 54 publications

(63 citation statements)

References 18 publications

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“…This finding was contrary to that of the previous study [23]. To our knowledge, only two small sample-sized studies by Shiroyama (N = 42) [23] and by Cortellini (N = 23) [24] evaluated PMI or SMI at the third lumber vertebra (L3) with PFS of PD-1 inhibitors for pretreated and advanced NSCLC, respectively. In the former Japanese study, the comparison between sarcopenic (low PMI) and non-sarcopenic (high PMI) patients detected significant differences in PFS, overall response rate and 1-year PFS rate [23].…”

Section: Discussioncontrasting

confidence: 72%

“…In the former Japanese study, the comparison between sarcopenic (low PMI) and non-sarcopenic (high PMI) patients detected significant differences in PFS, overall response rate and 1-year PFS rate [23]. However, probably owing to the small sample size, the latter Italian hypothesis-generating preliminary report failed to demonstrate significant differences in PFS and OS between low and high SMI [24]. Unlike these two studies, our study included five patients treated with PD-L1 inhibitor, atezolizumab, and more sarcopenic patients with low skeletal muscle quantity (72% of low PMI in our study vs. 52% of low PMI in Shiroyama's study, and 34.6% of low SMM in Cortellini's study).…”

Section: Discussionmentioning

confidence: 97%

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Sarcopenia and Visceral Adiposity Did Not Affect Efficacy of Immune-Checkpoint Inhibitor Monotherapy for Pretreated Patients With Advanced Non-Small Cell Lung Cancer

Minami¹,

Ihara²,

Tanaka³

et al. 2020

World J Oncol

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Background: This study aimed to investigate the association of computed tomography (CT)-assessed sarcopenia and visceral adiposity with efficacy and prognosis of immune-checkpoint inhibitor (ICI) therapy for pretreated non-small cell lung cancer (NSCLC). Methods: We retrospectively collected 74 patients with pretreated NSCLC who had initiated programmed cell death protein 1 (PD-1) or programmed cell death ligand 1 (PD-L1) inhibitor monotherapy between December 2015 and November 2018 at our hospital. As CT-assessed pretreatment markers, we used psoas muscle index (PMI), intramuscular adipose tissue content (IMAC), visceral-tosubcutaneous ratio (VSR) and visceral fat area (VFA) at lumbar vertebra L3 level. We divided 74 patients into high and low groups according to each Japanese sex-specific cutoff value. Using Kaplan-Meier curves and log-rank tests, we compared overall survival (OS) and progression-free survival (PFS). Adjusted by serum albumin, neutrophil-to-lymphocyte ratio, performance status and driver mutations, multivariate Cox proportional hazard analyses evaluated various variables as independent prognostic factors of OS and PFS. Results: We could not find significant difference in response rate (RR) and disease control rate (DCR) between low and high groups according to any factors. The OS of patients with body mass index (BMI) < 18.5 was significantly shorter than that of patients with BMI ≥ 18.5 (median 3.3 vs. 15.8 months, P < 0.01), while there was no significant difference in OS and PFS according to PMI, IMAC, VSR and VFA. Multivariate analyses detected no significant prognostic factor in OS and PFS, except for low IMAC (hazard ratio 0.43, 95% confidence interval 0.18-0.998, P = 0.0496) as a favorable prognostic factor of longer OS. Conclusions: Neither PMI nor VSR, VFA might be a significant prognostic factor of PFS and OS of ICI monotherapy for pretreated NSCLC. According to our multivariate analyses, IMAC was a significant prognostic factor of OS, but not of PFS. Thus, neither sarcopenia nor visceral adiposity may be associated with the efficacy of ICI therapy.

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Section: Discussioncontrasting

confidence: 72%

Section: Discussionmentioning

confidence: 97%

Sarcopenia and Visceral Adiposity Did Not Affect Efficacy of Immune-Checkpoint Inhibitor Monotherapy for Pretreated Patients With Advanced Non-Small Cell Lung Cancer

Minami¹,

Ihara²,

Tanaka³

et al. 2020

World J Oncol

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“…Recently, skeletal muscle mass has been included in prognostic score, which independently predicts survival in patients treated with anti PD-1/PD-L1 (programmed deadth-1/programmed death-ligand 1) agents 8 . In a preliminary report, we found that sarcopenic non-small cell lung cancer (NSCLC) patients receiving nivolumab had shorter progression free survival (PFS) and overall survival (OS) 9 . Moreover, other two retrospective studies found a significant association between sarcopenia, shorter PFS and worse objective response rate (ORR) 10,11 .…”

mentioning

confidence: 99%

Weighing the role of skeletal muscle mass and muscle density in cancer patients receiving PD-1/PD-L1 checkpoint inhibitors: a multicenter real-life study

Cortellini

Bozzetti

Palumbo

et al. 2020

Sci Rep

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Sarcopenia represents one of the hallmarks of all chronic diseases, including cancer, and was already investigated as a prognostic marker in the pre-immunotherapy era. Sarcopenia can be evaluated using cross-sectional image analysis of CT-scans, at the level of the third lumbar vertebra (L3), to estimate the skeletal muscle index (SMI), a surrogate of skeletal muscle mass, and to evaluate the skeletal muscle density (SMD). We performed a retrospective analysis of consecutive advanced cancer patient treated with PD-1/PD-L1 checkpoint inhibitors. Baseline SMI and SMD were evaluated and optimal cut-offs for survival, according to sex and BMI (+/−25) were computed. The evaluated clinical outcomes were: objective response rate (ORR), immune-related adverse events (irAEs), progression free survival (PFS) and overall survival (OS). From April 2015 to April 2019, 100 consecutive advanced cancer patients were evaluated. 50 (50%) patients had a baseline low SMI, while 51 (51%) had a baseline low SMD according to the established cut offs. We found a significant association between SMI and ECOG-PS (p = 0.0324), while no correlations were found regarding SMD and baseline clinical factors. The median follow-up was 20.3 months. Patients with low SMI had a significantly shorter PFS (HR = 1.66 [95% CI: 1.05-2.61]; p = 0.0291) at univariate analysis, but not at the multivariate analysis. They also had a significantly shorter OS (HR = 2.19 [95% CI: 1.31-3.64]; p = 0.0026). The multivariate analysis confirmed baseline SMI as an independent predictor for OS (HR = 2.19 [1.31-3.67]; p = 0.0027). We did not find significant relationships between baseline SMD and clinical outcomes, nor between ORR, irAEs and baseline SMI (data not shown). Low SMI is associated with shortened survival in advanced cancer patients treated with PD1/PDL1 checkpoint inhibitors. However, the lack of an association between SMI and clinical response suggests that sarcopenia may be generally prognostic in this setting rather than specifically predictive of response to immunotherapy.Sarcopenia is the condition of loss of muscle mass, with decreased muscle power, and it is one of the hallmarks of cancer, which negatively affects the most of clinical outcomes such as toxicities and survival 1 . The interactions must recognize also the lack of other adiposity metrics, such as the waist circumference, the waist-to-height ratio, and the body fat percentage. Moreover, the CT imaging analysis was limited by the data availability; indeed, the acquisition protocol was planned according to the presence of previous examination. conclusionOur finding of a significant shorter OS for low-SMI patients treated with PD-1/PD-L1 checkpoint inhibitors, suggests that sarcopenia might have a prognostic role, rather than predictive. However, to properly weighing our results, we must consider the significant association between poorer PS and low-SMI. Without making conclusive considerations, we can assume that after the advent of ICIs, we should give back further relevance to baseline nut...

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“…To our knowledge, no study has yet evaluated sarcopenia in the context of pembrolizumab treatment for melanoma using this simple method. Only limited research has been published on sarcopenia in patients treated with PD-1 inhibitors, yet existing evidence indicates that radiographic sarcopenia may be associated with higher frequency of toxicity and lower response rates (23,28). In contrast with these prior studies, no relationship between sarcopenia and treatment outcomes were identified in this study.…”

Section: Discussionmentioning

confidence: 99%

“…Clinicopathologic differences across BMI categories. After patients were divided into BMI groups as conducted in a prior study (23), 42 patients (27%) fell into the low/average BMI group (BMI less than 25), 56 patients (36%) were overweight (BMI greater than or equal to 25 and less than 30) and 58 patients (37%) were obese (BMI of 30 or greater). Other than the previously mentioned differences in sarcopenia rates, patients in the three BMI categories differed in sex, with obese patients being more likely to be men (p=0.047).…”

Section: Clinicopathologic Differences Across Sarcopenic Designationsmentioning

confidence: 99%

Higher BMI, But Not Sarcopenia, Is Associated With Pembrolizumab-related Toxicity in Patients With Advanced Melanoma

Ravichandran

Rushing

et al. 2020

Anticancer Res

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Background/Aim: To determine whether BMI and sarcopenia were related to treatment-limiting toxicity or efficacy of pembrolizumab treatment in melanoma patients. Patients and Methods: Medical records for melanoma patients undergoing pembrolizumab treatment at Duke University from January 2014 to September 2018 were reviewed. Pretreatment measurements such as BMI were collected. Pretreatment CT imaging was used to determine psoas muscle index (PMI). Patients in the lowest sex-specific tertile of PMI were sarcopenic. Logistic regression measured associations with treatment toxicity and response. Kaplan-Meier analysis assessed progression-free survival (PFS) and overall survival (OS). Results: Among 156 patients, the overall objective response rate was 46.2% and 29 patients (18.6%) experienced treatment-limiting toxicity. Sarcopenia was not significantly associated with toxicity, response, or survival. However, obese patients (BMI >30) experienced higher rates of toxicity (p=0.0007). Conclusion: Sarcopenia did not appear to predict clinically relevant outcomes. Obesity, however, represents a readily available predictor of pembrolizumab toxicity.

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Predictive value of skeletal muscle mass for immunotherapy with nivolumab in non‐small cell lung cancer patients: A “hypothesis‐generator” preliminary report

Cited by 54 publications

References 18 publications

Sarcopenia and Visceral Adiposity Did Not Affect Efficacy of Immune-Checkpoint Inhibitor Monotherapy for Pretreated Patients With Advanced Non-Small Cell Lung Cancer

Sarcopenia and Visceral Adiposity Did Not Affect Efficacy of Immune-Checkpoint Inhibitor Monotherapy for Pretreated Patients With Advanced Non-Small Cell Lung Cancer

Weighing the role of skeletal muscle mass and muscle density in cancer patients receiving PD-1/PD-L1 checkpoint inhibitors: a multicenter real-life study

Higher BMI, But Not Sarcopenia, Is Associated With Pembrolizumab-related Toxicity in Patients With Advanced Melanoma

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