Dataset Information

Association between body mass index and survival outcomes for cancer patients treated with immune checkpoint inhibitors: a systematic review and meta-analysis.

ABSTRACT:

Background

Immune checkpoint inhibitors (ICIs) have been increasingly applied in the treatment of several kinds of malignancies. Some clinical demographic characteristics were reported to be associated with the ICIs efficacy. The purpose of our current meta-analysis was to clearly evaluated the relationship between BMI and ICIs efficacy for cancer patients receiving immunotherapy.

Methods

A systematic search of Pubmed, EMBASE and conference proceedings was performed to investigate the influence of BMI on ICIs efficacy. Pooled analysis for overall survival (OS), progression-free survival (PFS) and immune-related adverse effects (IRAEs) were analyzed in current study.

Results

A total of 13 eligible studies comprising 5279 cancer patients treated with ICIs were included in the analysis. The pooled analysis showed there is positive association between high BMI and improved OS and PFS among patients with ICIs treatment (OS: HR?=?0.62, 95% CI 0.55-0.71, P?2?=?26.3%, P?=?0.202); PFS: HR?=?0.71, 95% CI 0.61-0.83, P?2?=?0%, P?=?0.591). There is no significant difference between the incidence of all grade IRAEs between obese, overweight patients and normal patients (Overweight vs Normal: pooled RR?=?1.28, 95% CI 0.76- 2.18, P?=?0.356; Obese vs Normal: pooled RR?=?1.36, 95% CI 0.85- 2.17, P?=?0.207).

Conclusion

An improved OS and PFS were observed in patients with high BMI after receiving ICIs treatment compared with patients of low BMI. No significant association between BMI and incidence of IRAEs was found in cancer patients after ICIs treatment.

SUBMITTER: An Y

PROVIDER: S-EPMC7291531 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

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Publications

Association between body mass index and survival outcomes for cancer patients treated with immune checkpoint inhibitors: a systematic review and meta-analysis.

An Yue Y Wu Zhonghua Z Wang Ningning N Yang Zhidong Z Li Yue Y Xu Boyang B Sun Mingjun M

Journal of translational medicine 20200612 1

<h4>Background</h4>Immune checkpoint inhibitors (ICIs) have been increasingly applied in the treatment of several kinds of malignancies. Some clinical demographic characteristics were reported to be associated with the ICIs efficacy. The purpose of our current meta-analysis was to clearly evaluated the relationship between BMI and ICIs efficacy for cancer patients receiving immunotherapy.<h4>Methods</h4>A systematic search of Pubmed, EMBASE and conference proceedings was performed to investigate ...[more]

PMID: 32532255

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Project description:BackgroundOverweight and obese patients with solid tumors receiving anti-programmed cell death-1 (PD-1)/PD-ligand-1(PD-L1) immune checkpoint inhibitors exhibit improved survival and higher risk of immune-related adverse events (irAEs) than those with a normal body mass index (BMI). In classic Hodgkin lymphoma (cHL), the impact of BMI on survival and immune-related toxicity is unknown. We evaluated for the first time associations of BMI with survival and irAEs in patients with relapsed/refractory (RR)-cHL undergoing PD-1 blockade.MethodsData from a multicenter study on 133 patients treated with the anti-PD1 antibody nivolumab (July 2015-December 2016) were retrieved from a prospective database. Progression-free (PFS), overall survival (OS), incidence and severity of irAEs according to BMI categories were estimated by Kaplan-Meier method, landmark-analyses and Cox regressions.ResultsPatients, mostly males (63%, n = 84) with a median age of 35 years (range, 15-82), advanced stage (75%), B symptoms (63%), bulky disease (24%), a median of 4 previous treatments (range, 1-9), received a median of 18 nivolumab doses (range, 1-57). No statistically significant differences across BMI subgroups emerged as to PFS, with 1-year rates of 67.1% for both normal weight (n = 66; 49.6%) and overweight (n = 31; 23.3%) patients. Underweight (n = 12; 9%) and obese (n = 24; 18%) patients had a 1-year PFS of 54.5% and 49%, respectively. In survival analyses, BMI either as a continuous (P = 0.5) or categorical (P for trend = 0.63) variable failed to associate with PFS. Response rates and time-to-response did not cluster in any BMI subset. No BMI-related differences in OS emerged across normal, overweight and obese patients but underweight patients had the worst survival. Occurrence of irAEs of whatever severity did not statistically associate with BMI.ConclusionsIn patients with RR-cHL receiving nivolumab, no statistically significant differences emerged in response rates, PFS and OS across BMI categories of normal weight, overweight and obese. Overweight/obese patients did not display an increased risk of irAEs. The exquisite sensitivity to anti-PD-1 antibodies, the unique cytokine milieu and effector pathways triggered by nivolumab in cHL, may represent biologic 'equalizers' counteracting the immunoregulatory effects of adiposity. Differently from solid tumors, BMI is not associated with treatment efficacy and immune-related toxicity and does not represent a predictive tool for PD-1-targeted immunotherapies in cHL.

Project description:BackgroundProton pump inhibitors (PPIs) have been shown to regulate the gut microbiome and affect the response to immune checkpoint inhibitors (ICIs). Contradictory results on survival have been observed in patients concomitantly treated with ICIs and PPIs. We performed a systematic review and meta-analysis to determine the association between PPI use and survival outcomes in ICI-treated cancer patients.MethodsEMBASE, MEDLINE/PubMed, Cochrane Library databases, and major oncology conference proceedings were searched. Studies comparing overall survival (OS) and progression-free survival (PFS) between PPI-treated and PPI-free groups of ICI-treated cancer patients were included. Data regarding study and patient characteristics, ICI and PPI treatments, and survival outcomes were extracted. Hazard ratios (HRs) with 95% confidence interval (CI) were pooled using random effects models. Subgroup meta-analyses and meta-regressions were performed to explore possible factors of heterogeneity among the studies.ResultsA total of 33 studies were included, comprising 7383 ICI- and PPI-treated patients and 8574 ICI-treated and PPI-free patients. The pooled HR was 1.31 (95% CI, 1.19-1.44; p < 0.001) for OS and 1.30 (95% CI, 1.17-1.46; p < 0.001) for PFS, indicating a significant negative association between PPI use and survival in ICI-treated patients. Subgroup meta-analyses by factors including cancer type, ICI type, and time window of PPI use revealed that ICI and PPI use impacted survival in patients with non-small cell lung or urothelial cancer, patients treated with anti-PD-1/PD-L1 antibodies, and patients receiving PPI as baseline treatment or 60 days before ICI treatment initiation.ConclusionsPPI use in patients treated with ICIs was associated with shorter OS and PFS, especially in several specific subgroups of cancer patients. PPIs should be strictly controlled and appear to not impact survival if given temporarily after ICI initiation. These observations could provide the basis for clinical guidelines for concomitant PPI and ICI use.

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Project description:ImportanceIn science and medical research, extreme and dichotomous conclusions may be drawn based on whether the P value falls above or below the threshold. The fragility index (ie, the minimum number of changes from nonevents to events resulting in loss of statistical significance) captures the vulnerability of statistics in trials with binary outcomes. There are a growing number of clinical trials of immune checkpoint inhibitors (ICIs), as well as expanding eligibility for patients to receive them. The robustness of survival outcomes in randomized clinical trials (RCTs) should be evaluated using the fragility index extended to time-to-event data.ObjectiveTo calculate the fragility of survival data in RCTs evaluating ICIs.Design, setting, and participantsIn this cross-sectional study, data on phase 3 prospective RCTs investigating ICIs included in PubMed from inception until January 1, 2020, were extracted. Two- or three-group studies reporting results for overall survival were eligible for the survival-inferred fragility index (SIFI) calculation, which is the minimum number of reassignments of the best survivors from the interventional group to the control group resulting in loss of significance (defined as P < .05 by log-rank test). For nonsignificant results, a negative SIFI was calculated by reversing the direction of reassignment (from the control group to the interventional group).Main outcomes and measuresSurvival-inferred fragility index.ResultsA total of 45 phase 3 prospective RCTs (4 of which had 3 groups, for a total of 49 groups) were identified, of which 6 (13%) investigated anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) agents, 25 (56%) investigated anti-programmed cell death 1 (PD-1) agents, 12 (27%) investigated anti-programmed cell death 1 ligand 1 agents, and 3 (7%) investigated the combination of anti-CTLA-4 and anti-PD-1 agents. The median SIFI was 5 (interquartile range, -4 to 12) for the intention-to-treat analysis; for these trials, the SIFI was 1% or less of the total sample size in 17 of 49 populations (35%). In 25 of the 49 intention-to-treat populations (51%), the SIFI was less than the number of censored patients in the intervention group shortly after randomization (defined as <5% of the follow-up time).Conclusions and relevanceThis study suggests that many phase 3 RCTs evaluating ICI therapies have a low SIFI for overall survival, resulting in uncertainty regarding their potential clinical benefit. Although not a definitive solution for the problems arising from dichotomization, SIFI provides an additional means of assessing and communicating the strength of statistical conclusions.

Dataset Information

Association between body mass index and survival outcomes for cancer patients treated with immune checkpoint inhibitors: a systematic review and meta-analysis.

Background

Methods

Results

Conclusion

Publications

Association between body mass index and survival outcomes for cancer patients treated with immune checkpoint inhibitors: a systematic review and meta-analysis.

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