Dataset Information

The effect of metformin or dipeptidyl peptidase 4 inhibitors on clinical outcomes in metastatic non-small cell lung cancer treated with immune checkpoint inhibitors.

ABSTRACT:

Background

Preclinical data have shown the immunomodulatory effects of metformin and dipeptidyl peptidase 4 (DPP4) inhibitors in patients with diabetes. However, its clinical impact remains unclear in lung cancer.

Methods

Between 2017 and 2021, 466 patients received ICI monotherapy. Patients were categorized into concurrent (MET; metformin or combination of metformin and DPP4 inhibitor) and without concomitant (NMET; nonmetformin/DPP4 inhibitors) administration of metformin and DPP4 inhibitors groups at least 8 weeks before and during ICI therapy. The primary objectives were the objective response rate (ORR) and progression-free survival (PFS). The second objective was to evaluate the overall survival (OS) and the occurrence of immune-related adverse events (irAEs).

Results

Among 466 patients, 89 (19.0%) and 377 (81%) were categorized into the MET and NMET groups, respectively. MET group had a significantly higher ORR (MET group: 24.7% vs. NMET group: 14.8%, p = 0.025) and longer PFS than those in the NMET group (MET group 5.1 month vs. NMET group 2.8 months, p = 0.018). After patients were stratified based on the prior line of therapy and PD L1 expression status, the PFS of the second-line therapy and PD L1 ≥50 was significantly higher in the MET than in the NMET group. The proportion of patients experiencing all-grade irAEs was numerically higher in the MET group (19.1%) than in the NMET group (14.3%), without statistical significance (p = 0.382).

Conclusions

Concurrent use of metformin and DPP4 inhibitors with ICIs significantly improved the clinical outcomes without increasing the incidence of irAEs in NSCLC.

SUBMITTER: Yang J

PROVIDER: S-EPMC9807448 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

The effect of metformin or dipeptidyl peptidase 4 inhibitors on clinical outcomes in metastatic non-small cell lung cancer treated with immune checkpoint inhibitors.

Yang Jieun J Kim Se Hyun SH Jung Eun Hee EH Kim Sang-A SA Suh Koung Jin KJ Lee Ji Yun JY Kim Ji-Won JW Kim Jin Won JW Lee Jeong-Ok JO Kim Yu Jung YJ Lee Keun-Wook KW Kim Jee Hyun JH Bang Soo-Mee SM Lee Jong Seok JS

Thoracic cancer 20221109 1

<h4>Background</h4>Preclinical data have shown the immunomodulatory effects of metformin and dipeptidyl peptidase 4 (DPP4) inhibitors in patients with diabetes. However, its clinical impact remains unclear in lung cancer.<h4>Methods</h4>Between 2017 and 2021, 466 patients received ICI monotherapy. Patients were categorized into concurrent (MET; metformin or combination of metformin and DPP4 inhibitor) and without concomitant (NMET; nonmetformin/DPP4 inhibitors) administration of metformin and DP ...[more]

PMID: 36351567

Similar Datasets

Project description:Hyponatremia has been established as a prognostic indicator of survival in metastatic non-small cell lung cancer (mNSCLC). Conversely, the influence of normal sodium levels remains unexplored. This study aims to investigate the impact of natremia in mNSCLC patients undergoing treatment with immune checkpoint inhibitors (ICIs). Clinical and biochemical data of patients treated with ICIs for mNSCLC were obtained. Availability of baseline sodium values was a study inclusion criterion. Patients were categorized into two groups based on the cut off sodium value, determined using the receiver operating characteristic curve. Subsequently, the influence of sodium levels on response rate (RR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS) was analyzed. PFS and OS were assessed via the Kaplan-Meier method. Univariate and multivariate Cox regression analyses were conducted to evaluate prognostic factors for PFS and OS. The analysis included 88 patients, of whom 73.1% were men, with a median age of 71 years (range, 47-91). A comparison between patients with baseline natremia ≥ 140 mEq/L (n = 43) and those with < 140 mEq/L (n = 45) revealed PFS durations of 7.0 vs. 2.1 months (p < .01) and OS durations of 15.6 vs. 6.8 months, respectively (p = .02). In the univariate survival analysis, pre-ICI serum sodium ≥ 140 mEq/L (p = .01) was associated with improved PFS, while factors associated with OS included brain metastasis (p = .05) and pre-ICI serum sodium ≥ 140 mEq/L (p = .02). In the multivariate analysis, pre-ICI serum sodium ≥ 140 mEq/L maintained a statistically significant association with OS (p = .04)..This study represents the first investigation into the impact of normonatremia in mNSCLC. Our findings suggest that serum sodium levels < 140 mEq/L at baseline and initial assessment are independently associated with poorer PFS and OS in mNSCLC patients undergoing first-line treatment with ICIs.

Project description:BackgroundImmune checkpoint inhibitors (ICIs) have revolutionized the treatment of non-small-cell lung cancer (NSCLC). Denosumab is a humanized monoclonal antibody to RANK ligand used to prevent skeletal-related events of bone metastases in solid tumors. We are reporting the clinical outcomes in our NSCLC patients who received RANKL inhibitor in combination with ICIs.MethodsThis observational study used retrospective data from a tertiary cancer center from 2015-2020. Stage IV non-small cell lung cancer patients who received denosumab within 30 days of ICIs (pembrolizumab, nivolumab, atezolizumab, ipilimumab) were included. Kaplan-Meier curves were obtained for survival analysis.ResultsWe identified 69 patients and all had skeletal metastases, and 37.7% had brain metastases. Median OS was 6.3 months and median PFS was 2.8 months, with overall response rate (ORR) of 18.8% and disease control rate (DCR) of 40.6%. Median OS in patients with concomitant denosumab and ICIs more than 3 months was 11.5 months, comparing to 3.6 months in patients with <3 months of concomitant therapy (P=0.0005). OS and PFS did not differ with respect to brain metastases or number of skeletal metastases. However, the duration of ICIs and denosumab overlap was associated with improved OS and PFS. Among the 18.8% of patients who achieved complete response (CR) and partial response (PR), six-month survival rate was 100% and one-year survival rate was 69.2%. Most of the patients tolerated denosumab well, and hypocalcemia was the most commonly reported side effect.ConclusionsPatients receiving combination therapy did not perform poorly comparing to published studies despite of poor prognostic features such as brain metastases and numerous skeletal metastases. Although we did notice potential benefit of the longer duration of concomitant use of ICI and denosumab, future prospective clinical trials are needed to evaluate the synergistic effect of RANKL inhibitors/ICI and if duration of RANKL inhibitors matters.

Project description:ObjectiveThe aim of this meta-analysis was to summarize the available results of immunotherapy predictors for small cell lung cancer (SCLC) and to provide evidence-based information for their potential predictive value of efficacy.MethodsWe searched PubMed, EMBASE, Web of Science, The Cochrane Library, and ClinicalTrials (from January 1, 1975 to November 1, 2021). The hazard ratios (HR) and its 95% confidence intervals (CIs) and tumor response rate of the included studies were extracted.ResultsEleven studies were eventually included and the pooled results showed that programmed cell death ligand 1 (PD-L1) positive: objective response rate (ORR) (relative risk [RR] = 1.39, 95% CI [0.48, 4.03], p = 0.54), with high heterogeneity (p = 0.05, I2 = 56%); disease control rate [DCR] (RR = 1.31, 95% CI [0.04, 38.57], p = 0.88), with high heterogeneity (p = 0.04, I2 = 75%); overall survival (OS) (HR = 0.89, 95% CI [0.74, 1.07], p = 0.22); and progression-free survival (PFS) (HR = 0.83, 95% CI [0.59, 1.16], p = 0.27), with high heterogeneity (p = 0.005, I2 = 73.1%). TMB-High (TMB-H): OS (HR = 0.86, 95% CI [0.74, 1.00], p = 0.05); PFS (HR = 0.71, 95% CI [0.6, 0.85], p < 0.001). Lactate dehydrogenase (LDH) >upper limit of normal (ULN): OS (HR = 0.95, 95% CI [0.81, 1.11], p = 0.511). Asian patients: OS (HR = 0.87, 95% CI [0.72, 1.04], p = 0.135); White/Non-Asian patients: OS (HR = 0.83, 95% CI [0.76, 0.90], p < 0.001). Liver metastasis patients: OS (HR = 0.93, 95% CI [0.83, 1.05], p = 0.229); PFS (HR = 0.84, 95% CI [0.67, 1.06], p = 0.141). Central nervous system (CNS) metastasis patients: OS (HR = 0.91, 95% CI [0.71, 1.17], p = 0.474); PFS (HR = 1.03, 95% CI [0.66, 1.60], p = 0.903).ConclusionThe available research results do not support the recommendation of PD-L1 positive and TMB-H as predictors for the application of immune checkpoint inhibitors (ICIs) in SCLC patients. LDH, baseline liver metastasis and CNS metastasis may be used as markers/influencing factors for predicting the efficacy of ICIs in SCLC patients. Non-Asian SCLC patients had better efficacy with ICIs in our results.

Dataset Information

The effect of metformin or dipeptidyl peptidase 4 inhibitors on clinical outcomes in metastatic non-small cell lung cancer treated with immune checkpoint inhibitors.

Background

Methods

Results

Conclusions

Publications

The effect of metformin or dipeptidyl peptidase 4 inhibitors on clinical outcomes in metastatic non-small cell lung cancer treated with immune checkpoint inhibitors.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets