scholarly journals Impact of Antibiotics and Proton Pump Inhibitors on Efficacy and Tolerance of Anti-PD-1 Immune Checkpoint Inhibitors

2021 ◽  
Vol 12 ◽  
Author(s):  
Quentin Giordan ◽  
Julia Salleron ◽  
Catherine Vallance ◽  
Clothilde Moriana ◽  
Christelle Clement-Duchene
Keyword(s):  
Adverse Events ◽  
Proton Pump Inhibitors ◽  
Proton Pump ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Small Cell Lung Carcinoma ◽  
Progression Free Survival ◽  
Cell Lung Carcinoma ◽  
The Impact

BackgroundThe use of antibiotics (ATB) and proton-pump inhibitors (PPI) alters the composition and diversity of the gut microbiota, which can influence the immune system, consequently interfering with response to anti-PD1 immune checkpoint inhibitors (ICI). We assessed the impact of ATB and/or PPI use on the efficacy and safety of ICI.MethodsTwo hundred twelve patients treated with anti-PD1 ICI for non-small cell lung carcinoma, melanoma, upper airway & digestive tract carcinoma or renal cell carcinoma were retrospectively included. Patients having received ATB within 60 days before ICI initiation were included in the ATB+ group. Patients having received PPI within 30 days before ICI initiation were included in the PPI+ group. Four groups were thus considered: ATB-/PPI-, ATB+/PPI-, ATB-/PPI+, ATB+/PPI+. Response rate was assessed by RECIST v1.1. Overall survival (OS), progression-free survival (PFS) and adverse events, recorded using Common Terminology Criteria for Adverse Events Version 5, were compared using inverse probability of treatment weighting to account for selection bias.ResultsPFS at 6 months was 56.7 %, 95%CI (49.6%; 63.2%) and 47.2 %, 95%CI (39.8%;54.1%) at 12 months. OS was 81.6%, 95%CI (75.6%; 86.2%) at 6 months, and 69.4%, 95%CI (61.9%;75.7%) at 12 months. Compared to ATB-/PPI- group, PFS was lower for the ATB+/PPI- group [Hazard ratio (HR) 1.90, 95%CI (1.41;2.57)] and the ATB-/PPI+ group [HR 1.51, 95%CI (1.11;2.05)], and lowest in the ATB+/PPI+ group [HR 3.65, 95%CI (2.75;4.84)]. For OS, the use of ATB alone or PPI alone or in combination was a risk factor for death, with each increasing HR values by a similar magnitude, and the combination of ATB and PPI did not increase risk further. AEs were observed in 78 cases (36.8%) with no significant impact of ATB or PPI use.ConclusionsThis study reveals that ATB and/or PPI use can alter response to anti-PD1 ICI, and the prognosis of cancer patients. The microbiota mechanisms involved in the response to ICI should be investigated to optimize patient management.

Assessment of hospitalization rates for immune-related adverse events with immune checkpoint inhibitors

2020 ◽  
pp. 107815522096890
Author(s):  
Laura Nice ◽  
Ryan Bycroft ◽  
Xiaoyong Wu ◽  
Shesh N Rai ◽  
Lindsay Figg ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Adverse Events ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Progression Free Survival ◽  
Median Length ◽  
Number Of Patients ◽  
Grade 3 ◽  
The Impact

Introduction Immune checkpoint inhibitors (ICIs) have become the standard of care in many cancer types. As the number of patients receiving ICIs for various cancers continues to expand, patients and practitioners should be aware of potentially severe immune-related adverse events (irAEs). Despite reports of the incidence of grade 3/4 toxicities, the proportion of patients whose symptoms were clinically severe enough to warrant hospitalization for adverse event management is unknown. Methods This single center, retrospective, observational study was designed to determine the impact of irAEs on patients and the hospital. Patients who started ICIs from May 2016 through May 2019 for melanoma or lung cancer were included. The primary outcome was incidence of hospitalization for irAE. Secondary outcomes included median length of hospitalization, time to onset of irAE, rates of hospitalization for irAE per each checkpoint inhibitor regimen, organ system affected, progression free survival, and overall survival. Results Of 384 patients with melanoma or lung cancer, 27 (7%) were hospitalized at our institution for an irAE. The most common irAE leading to hospitalization was colitis for patients with melanoma and pneumonitis for patients with lung cancer. The median length of stay across all hospitalizations was 10 days. Twenty-five patients required the use of corticosteroids while hospitalized, while eight of these patients required second line irAE treatment. For the total patient population, 34.7% experienced a grade 1/2 irAE and 13.1% experienced a grade 3/4 irAE. Conclusion Our cohort of patients experienced similar rates irAEs as reported in clinical trials and published reports.

Metabolic disease and adverse events from immune checkpoint inhibitors

2021 ◽  
Author(s):  
Amanda Leiter ◽  
Emily Carroll ◽  
Sonia De Alwis ◽  
Danielle Brooks ◽  
Jennifer Ben Shimol ◽  
...  
Keyword(s):  
Metabolic Disease ◽  
Adverse Events ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Metabolic Diseases ◽  
Checkpoint Inhibitors ◽  
Normal Weight ◽  
Metabolic Risk ◽  
The Impact ◽  
Metabolic Comorbidities

Objective: Obese and overweight body mass index (BMI) categories have been associated with increased immune-related adverse events (irAEs) in patients with cancer receiving immune checkpoint inhibitors (ICIs); however, the impact of being overweight in conjunction with related metabolic syndrome-associated factors on irAEs have not been investigated. We aimed to evaluate the impact of overweight and obese BMI according to metabolic disease burden on the development of irAEs. Design and Methods: We conducted a retrospective observational study of patients receiving ICIs at a cancer center. Our main study outcome was development of grade 2 (moderate) irAEs. Our main predictor was weight/metabolic disease risk category: (1) normal weight (BMI 18.5-24.9 kg/m2)/low metabolic risk (<2 metabolic diseases [diabetes, dyslipidemia, hypertension] ), (2) normal weight/high metabolic risk (2 metabolic diseases), (3) overweight (BMI 25 kg/m2)/low metabolic risk, and (4) overweight/high metabolic risk. Results: Of 411 patients in our cohort, 374 were eligible for analysis. Overall, 111 (30%) patients developed grade 2 irAEs. In Cox analysis, overweight/low metabolic risk was significantly associated with grade 2 irAEs (hazard ratio [HR]: 2.0, 95% confidence interval [95% CI]: 1.2-3.4) when compared to normal weight/low metabolic risk, while overweight/high metabolic risk (HR: 1.3, 95% CI: 0.7-2.2) and normal weight/high metabolic risk (HR: 1.5, 95% CI: 0.7-3.0) were not. Conclusions: Overweight patients with fewer metabolic comorbidities were at increased risk for irAEs. This study provides an important insight that BMI should be evaluated in the context of associated metabolic comorbidities in assessing risk of irAE development and ICI immune response.

scholarly journals Efficacy of immune checkpoint inhibitors and age in cancer patients

Immunotherapy ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 587-603 ◽  
Author(s):  
Xuan-zhang Huang ◽  
Peng Gao ◽  
Yong-xi Song ◽  
Jing-xu Sun ◽  
Xiao-wan Chen ◽  
...  
Keyword(s):  
Cancer Patients ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Progression Free Survival ◽  
Comparable Efficacy ◽  
Control Groups ◽  
Free Survival ◽  
Meta Regression Analysis ◽  
The Impact

Aim: To evaluate the impact of age on the efficacy of immune checkpoint inhibitors (ICI) in cancer patients. Materials & methods: The primary outcomes included overall survival (OS) and progression-free survival (PFS). Subgroup, meta-regression analysis and within-trial interaction HR were conducted. Results: A total of 34 studies containing 20,511 cancer patients were included. ICI could improve the OS and PFS in patient aged <65 and ≥65 years. Patients aged <75 years treated with ICI also had favorable OS and PFS compared with the control groups. Conclusion: ICI has comparable efficacy in cancer patients aged <65 and ≥65 years. Cancer patients aged ≥75 years need more attention in the future clinical trials.

scholarly journals Concomitant Proton Pump Inhibitors and Immune Checkpoint Inhibitors Increase Nephritis Frequency

In Vivo ◽  
2021 ◽  
Vol 35 (5) ◽  
pp. 2831-2840
Author(s):  
KOKI KATO ◽  
TOMOHIRO MIZUNO ◽  
TAKENAO KOSEKI ◽  
YOSHIMASA ITO ◽  
MASAKAZU HATANO ◽  
...  
Keyword(s):  
Proton Pump Inhibitors ◽  
Proton Pump ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors

scholarly journals The effect of antibiotics on the clinical outcomes of patients with solid cancers undergoing immune checkpoint inhibitor treatment: a retrospective study

BMC Cancer ◽  
2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Hyunho Kim ◽  
Ji Eun Lee ◽  
Sook Hee Hong ◽  
Myung Ah. Lee ◽  
Jin Hyoung Kang ◽  
...  
Keyword(s):  
Retrospective Study ◽  
Clinical Outcomes ◽  
Immune Checkpoint ◽  
Checkpoint Inhibitors ◽  
Small Cell Lung Carcinoma ◽  
Objective Response ◽  
Progression Free Survival ◽  
Solid Cancer ◽  
Cell Lung Carcinoma ◽  
Antibiotics Use

Abstract Background This study aimed to assess the effect of antibiotics on the clinical outcomes of patients with solid cancers undergoing treatment with immune checkpoint inhibitors (ICIs). Methods The medical records of 234 patients treated with ICIs for any type of solid cancer between February 2012 and May 2018 at the Seoul St. Mary’s Hospital were retrospectively reviewed. The data of patients who received antibiotics within 60 days before the initiation of ICI treatment were analyzed. The patients’ responses to ICI treatment and their survival were evaluated. Results Non-small-cell lung carcinoma was the most common type of cancer. About half of the patients were treated with nivolumab (51.9%), and cephalosporin (35.2%) was the most commonly used class of antibiotics. The total objective response rate was 21%. Antibiotics use was associated with a decreased objective response (odds ratio 0.466, 95% confidence interval [CI] 0.225–0.968, p = 0.040). The antibiotics group exhibited shorter progression-free survival (PFS) and overall survival (OS) than the no antibiotics group (median PFS: 2 months vs. 4 months, p < 0.001; median OS: 5 months vs. 17 months, p < 0.001). In the multivariate analysis, antibiotics use was a significant predictor of patient survival (PFS: hazard ratio [HR] 1.715, 95% CI 1.264–2.326, p = 0.001; OS: HR 1.785, 95% CI 1.265–2.519, p = 0.001). Conclusions The use of antibiotics may affect the clinical outcomes of patients with solid cancers treated with ICIs. Careful prescription of antibiotics is warranted in candidates who are scheduled for ICI treatment. Trial registration Not applicable (retrospective study).

Efficacy of immune checkpoint inhibitors in patients with brain metastasis from NSCLC, RCC, and melanoma.

2018 ◽  
Vol 36 (5_suppl) ◽  
pp. 214-214 ◽  
Author(s):  
Adam Lauko ◽  
Bicky Thapa ◽  
Xuefei Jia ◽  
Manmeet Singh Ahluwalia
Keyword(s):  
Brain Metastasis ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Small Cell Lung Carcinoma ◽  
Tertiary Care ◽  
Multivariable Analysis ◽  
Volumetric Analysis ◽  
Cell Lung Carcinoma ◽  
Combination Methods

214 Background: Immune checkpoint inhibitors are revolutionizing the treatment of multiple advanced malignancies, however, there is limited data on the efficacy of immune checkpoint blockade in brain metastasis. We conducted a study to analyze the overall survival (OS) and progression-free survival (PFS) among patients with brain metastasis from Non-Small Cell Lung Carcinoma (NSCLC), Renal Cell Carcinoma (RCC), and Melanoma treated with either Nivolumab, Pembrolizumab, Ipilimumab or a combination. Methods: After IRB approval, we retrospectively evaluated patients with brain metastasis treated at our tertiary care institution from 2011-2017 who underwent immunotherapy and one or more of the following; whole brain radiation therapy (WBRT), surgery, stereotactic radiosurgery (SRS) or systemic chemotherapy. Univariable and multivariable analysis was utilized to analyze OS and PFS. Volumetric analysis to assess treatment response is ongoing. Results: A total of 128 patients were identified with a median age of 60.6 years. 49% of patients were male; 77% of patients had a good (0 or 1) ECOG performance scores at the time of the brain metastasis; 83 patients had supratentorial brain metastasis, 11 had infratentorial and 24 had both. The prevalence of mutations was 34% in NSCLC patients, 58% in melanoma, and 0% in RCC. The median OS from the start of immunotherapy was not reached for RCC and was 17.1 and 28.9 months for Melanoma and NSCLC respectively. Median PFS was 5.9, 6.7 and 3.6 months for RCC, Melanoma, and NSCLC respectively. On multivariable analysis, SRS, sex and the number of cycles of immunotherapy had statistically significant hazard ratios. Conclusions: Immune checkpoint inhibitors are efficacious in the treatment of brain metastasis. Further analysis including response criteria using volumetric analysis is ongoing and final results will be presented at the meeting. [Table: see text]

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