Protective effect of obesity on survival in cancers treated with immunotherapy vanishes when controlling for type of cancer, weight loss and reduced skeletal muscle

Antoun, Sami; Lanoy, Émilie; Farhane, Siham; Martin, Lisa W.; Robert, Caroline; Planchard, David; Routier, Émilie; Voisin, Anne Laure; Messayke, Sabine; Champiat, Stéphane; Michot, Jean Marie; Laghouati, Salim; Lambotte, Olivier; Marabelle, Aurélien; Baracos, Vickie E.

doi:10.1016/j.ejca.2022.10.013

Cited by 19 publications

(17 citation statements)

References 39 publications

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“…In our study, we found the high BMI level was correlated with better OS and PFS in NSCLC patients, but failed to independently predict the clinical outcome in the multivariate analysis. A recent study has found the association between BMI level and the survival of ICI-treated patients may be affected by some clinical confounders, which partly explains the inconsistent results in our study (49). Moreover, a narrative review has implied the unreliability of BMI as a clinical indicator for lung cancer patients and recommended novel radiological strategies to define obesity (50).…”

Section: Discussionmentioning

confidence: 75%

Identification of prognostic nutritional index as a reliable prognostic indicator for advanced lung cancer patients receiving immune checkpoint inhibitors

et al. 2023

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BackgroundPrognostic nutritional index (PNI) has been identified as a reliable prognostic factor for cancer adjuvant therapy. However, its prognostic value in lung cancer patients receiving immune checkpoint inhibitors (ICIs) remains inconclusive.MethodA systematic literature review and meta-analysis was performed based on online databases before March 1th 2023. The correlation of PNI with overall survival (OS) or progression-free survival (PFS) was determined using the hazard ratios (HRs) coupled with 95% confidence intervals (CIs). Then, a retrospective cohort enrolling 123 ICI-treated lung cancer patients from two hospitals was utilized for validation and further investigation.ResultsA total of 14 studies enrolling 1,260 lung cancer patients were included in the meta-analysis. The high PNI level was significantly correlated with better OS (HR = 2.56, 95% CI = 1.86–3.54) and PFS (HR = 1.91, 95% CI = 1.53–2.40) of the lung cancer patients. The subgroup analysis confirmed the results except for the PFS in patients receiving anti-PD-1 therapy (HR = 1.51, 95% CI = 0.86–2.65). In the retrospective study, the high PNI level was identified as a favorable factor for OS and PFS not only in the whole cohort but also in the subgroups stratified by non-small cell lung cancer and small cell lung cancer. The high PNI was also correlated with better anti-cancer therapy response and performed better than body mass index and serum albumin level in OS prediction. Finally, we established a novel prognostic nomogram based on PNI and other clinical parameters. The nomogram was found to perform well in predicting the 1-year OS of ICI-treated lung cancer patients.ConclusionBoth the meta-analysis and retrospective work demonstrate the PNI is a reliable prognostic factor for advanced lung cancer patients receiving ICI-based therapies. Our study further highlights the crucial role of nutrition assessment and intervention in cancer immunotherapy.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/, identifier: CRD42023424146.

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Section: Discussionmentioning

confidence: 75%

Identification of prognostic nutritional index as a reliable prognostic indicator for advanced lung cancer patients receiving immune checkpoint inhibitors

et al. 2023

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“…Weight loss prior to ICI treatment which was not available in this study, should be considered as another potentially influential confounding factor, given its prognostic significance in patients with NSCLC. 34 Further investigation is necessary to explore this relationship in more detail and specificity.…”

Section: Discussionmentioning

confidence: 99%

Obesity paradox in patients with non‐small cell lung cancer undergoing immune checkpoint inhibitor therapy

Lee,

Kang,

Ahn

et al. 2023

J cachexia sarcopenia muscle

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BackgroundThe obesity paradox in patients with advanced non‐small cell lung cancer receiving immune checkpoint inhibitor therapy has been observed, but its underlying mechanism is not fully understood. We aimed to investigate whether body composition affects the prognostic impact of obesity, as determined by body mass index (BMI), on survival.MethodsThis retrospective study evaluated the data collected from Asian patients who were treated with immune checkpoint inhibitors for advanced non‐small cell lung cancer between October 2015 and October 2021. We used abdominal cross‐sectional imaging to calculate the skeletal muscle and visceral fat indices (cm2/m2) by dividing the cross‐sectional areas of the skeletal muscle and visceral fat by the height squared. Cox proportional‐hazards regression was performed to determine the correlation between BMI according to the Asia‐Pacific classification, body composition metrics and overall survival.ResultsWe analysed the data of 820 patients (630 men and 190 women, with a mean age of 64.3 years [standard deviation: 10.4 years]) and observed 572 (69.8%) deaths with the 1‐year mortality rate of 0.58 (95% confidence interval, 0.55–0.62). Obese BMI was associated with longer overall survival, independent of clinical covariates (hazard ratio, 0.64; 95% confidence interval: 0.52–0.80). The prognostic value of obese BMI remained after additional adjustments for skeletal muscle index (hazard ratio, 0.68; 95% confidence interval, 0.53–0.87) or visceral fat index (hazard ratio, 0.54; 95% confidence interval: 0.41–0.70). No association was observed between sex and the impact of BMI on overall survival (P‐value for interaction >0.05).ConclusionsIn Asian patients with advanced non‐small cell lung cancer who received immune checkpoint inhibitors, obese BMI was associated with favourable overall survival independent of skeletal muscle or visceral fat mass.

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“…Better identification of patients likely to benefit from immunotherapy is clearly needed. Recent studies report conflicting findings on the influence of sex and BMI on response to ICIs 5 – 11 , 25 – 30 , 32 – 34 , while emerging evidence suggests a potential link between cachexia status and poor response to ICIs 12 – 15 , 18 . In this retrospective study, we evaluated the effects of sex, BMI and PWL on outcomes in metastatic NSCLC patients treated with ICIs as part of standard of care at our institution.…”

Section: Discussionmentioning

confidence: 99%

“…Similarly, PWL has been reported in some studies to be associated with worse outcome in those receiving chemoimmunotherapy 10 , 16 , 17 Sarcopenia, or low muscle mass, may also contribute to poor ICI response. A recent study found that the protective effect of BMI on survival in melanoma and NSCLC patients disappeared after accounting for weight loss and skeletal muscle index 18 . However, other studies of skeletal muscle mass using cross-sectional imaging of computerized-tomography (CT) scans to predict ICI outcomes have yielded mixed results 19 – 22 .…”

Section: Introductionmentioning

confidence: 99%

Male sex and pretreatment weight loss are associated with poor outcome in patients with advanced non-small cell lung cancer treated with immunotherapy: a retrospective study

Jin,

Visina,

Burns

et al. 2023

Sci Rep

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The influence of sex and body mass index (BMI) on the efficacy of immune checkpoint inhibitors (ICIs) in advanced non-small cell lung cancer (NSCLC) patients remains unclear. We conducted a retrospective study to evaluate the relationship between sex, BMI, pretreatment weight loss (PWL), and clinical outcomes in 399 stage IV NSCLC patients treated with ICIs using data abstracted from medical records. Multivariable Cox proportional hazards models were used to assess the impact on overall survival and progression-free survival. Females were significantly more likely to experience immune-related adverse events and had a significantly lower risk of death compared to males in our patient cohort. In stratified analyses, the latter was limited to those receiving first-line monotherapy. BMI was overall not significantly associated with outcome. However, underweight patients had a significantly higher risk of both progression and death compared to normal weight patients in the first-line monotherapy group. When stratified by sex, underweight males had a significantly higher risk of progression and death compared to normal weight males. This was not observed among females. Those with PWL had overall significantly worse outcomes compared to those without. In stratified analyses, PWL was associated with significantly worse OS in both females and males. Stratified by treatment, the worse outcome was limited to those receiving ICI monotherapy. In summary, utilizing real-world data, this study suggests that male sex, being underweight, and PWL negatively impact ICI efficacy in NSCLC patients. Therapeutic approaches to improve ICI outcomes in underweight patients and those with PWL should be investigated.

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Protective effect of obesity on survival in cancers treated with immunotherapy vanishes when controlling for type of cancer, weight loss and reduced skeletal muscle

Cited by 19 publications

References 39 publications

Identification of prognostic nutritional index as a reliable prognostic indicator for advanced lung cancer patients receiving immune checkpoint inhibitors

Identification of prognostic nutritional index as a reliable prognostic indicator for advanced lung cancer patients receiving immune checkpoint inhibitors

Obesity paradox in patients with non‐small cell lung cancer undergoing immune checkpoint inhibitor therapy

Male sex and pretreatment weight loss are associated with poor outcome in patients with advanced non-small cell lung cancer treated with immunotherapy: a retrospective study

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