Impact of concomitant medications on the efficacy of immune checkpoint inhibitors: an umbrella review
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SUBMITTER: Li H
PROVIDER: S-EPMC10570520 | biostudies-literature | 2023 Jan
REPOSITORIES: biostudies-literature
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Project description:In the Modern era, immune checkpoint inhibitors (ICIs) have been the cornerstone of success in the treatment of several malignancies. Despite remarkable therapeutic advances, complex matrix together with significant molecular and immunological differences have led to conflicting outcomes of ICI therapy in gastrointestinal (GI) cancers. As far we are aware, to date, there has been no study to confirm the robustness of existing data, and this study is the first umbrella review to provide a more comprehensive picture about ICIs' efficacy and safety in GI malignancies. Systematic search on PubMed, Scopus, Web of Science, EMBASE, and Cochrane library identified 14 meta-analyses. The pooled analysis revealed that ICIs application, especially programmed death-1 (PD-1) inhibitors such as Camrelizumab and Sintilimab, could partially improve response rates in patients with GI cancers compared to conventional therapies. However, different GI cancer types did not experience the same efficacy; it seems that hepatocellular carcinoma (HCC) and esophageal cancer (EC) patients are likely better candidates for ICI therapy than GC and CRC patients. Furthermore, application of ICIs in a combined-modal strategy are perceived opportunity in GI cancers. We also assessed the correlation of PD-L1 expression as well as microsatellite status with the extent of the response to ICIs; overall, high expression of PD-L1 in GI cancers is associated with better response to ICIs, however, additional studies are required to precisely elaborate ICI responses with respect to microsatellite status in different GI tumors. Despite encouraging ICI efficacy in some GI cancers, a greater number of serious and fatal adverse events have been observed; further highlighting the fact that ICI therapy in GI cancers is not without cost, and further studies are required to utmost optimization of this approach in GI cancers.
| S-EPMC10771001 | biostudies-literature
Project description:Aim: Patients receiving checkpoint inhibitors (CPI) are frequently on other medications for co-morbidities. We explored the impact of concomitant medication use on outcomes. Materials & methods: 210 metastatic cancer patients on CPI were identified and association between concomitant medication use and immune-related adverse events with clinical outcomes was determined. Results: Aspirin, metformin, β-blockers and statins were not shown to have any statistically significant difference on clinical benefit. 26.3% patients with clinical benefit developed rash versus 11.8% without clinical benefit (p < 0.05) on multivariate analysis. Conclusion: Use of common prescription and nonprescription medications in patients with multiple co-morbidities appears safe and does not have an adverse effect on CPI efficacy. The presence of rash predicted for a better response.
| S-EPMC7202260 | biostudies-literature
Project description:There are multiple approved indications for immune checkpoint inhibitors (ICI) in patients with advanced solid tumors. Polypharmacy, defined as the use of ≥ 5 medications, is common among cancer patients. The impact of these non-oncologic medications on ICI efficacy or the development of side effects, specifically immune related adverse events (irAEs), is unclear. Recent clinical studies investigating the connection between concomitant medications and ICI efficacy have produced conflicting results. A systematic literature search was performed on PubMed to identify published clinical studies evaluating the impact of metformin, angiotensin-converting-enzyme inhibitor (ACEi), angiotensin receptor blockers (ARBs) and aspirin on ICI outcomes and toxicity in patients with advanced solid tumors. Clinical outcomes assessed included overall response rate, progression free survival, overall patient survival and the development of adverse events, specifically irAEs. A total of 10 retrospective studies were identified. Most studies reported a small percentage (range 8% to 42%) of their study population taking the concomitant medications of interest. Collectively, the studies did not identify a significant impact on ICI efficacy with concomitant medication use. In addition, the impact on irAEs was rarely reported in these studies but no significant group effect on reported toxicities or irAEs was found. This review provides a comprehensive analysis of current clinical studies and illustrates potential alterations in the tumor microenvironment induced by the medications. Given the high occurrence of polypharmacy among patients with advanced cancer, gaining a better understanding of the impact of non-oncologic medications on immunotherapy is necessary to improve ICI efficacy and reduce toxicity.
| S-EPMC9196183 | biostudies-literature
Project description:BackgroundImmune checkpoint inhibitors (ICIs) have revolutionized the management of advanced melanoma (AM). However, data on ICI effectiveness have largely been restricted to clinical trials, thereby excluding patients with co-existing malignancies. Chronic lymphocytic leukemia (CLL) is the most prevalent adult leukemia and is associated with increased risk of melanoma. CLL alters systemic immunity and can induce T-cell exhaustion, which may limit the efficacy of ICIs in patients with CLL. We, therefore, sought to examine the efficacy of ICI in patients with these co-occurring diagnoses.Patients and methodsIn this international multicenter study, a retrospective review of clinical databases identified patients with concomitant diagnoses of CLL and AM treated with ICI (US-MD Anderson Cancer Center, N = 24; US-Mayo Clinic, N = 15; AUS, N = 19). Objective response rates (ORRs), assessed by RECIST v1.1, and survival outcomes [overall survival (OS) and progression-free survival (PFS)] among patients with CLL and AM were assessed. Clinical factors associated with improved ORR and survival were explored. Additionally, ORR and survival outcomes were compared between the Australian CLL/AM cohort and a control cohort of 148 Australian patients with AM alone.ResultsBetween 1997 and 2020, 58 patients with concomitant CLL and AM were treated with ICI. ORRs were comparable between AUS-CLL/AM and AM control cohorts (53% versus 48%, P = 0.81). PFS and OS from ICI initiation were also comparable between cohorts. Among CLL/AM patients, a majority were untreated for their CLL (64%) at the time of ICI. Patients with prior history of chemoimmunotherapy treatment for CLL (19%) had significantly reduced ORRs, PFS, and OS.ConclusionsOur case series of patients with concomitant CLL and melanoma demonstrate frequent, durable clinical responses to ICI. However, those with prior chemoimmunotherapy treatment for CLL had significantly worse outcomes. We found that CLL disease course is largely unchanged by treatment with ICI.
| S-EPMC11289780 | biostudies-literature
Project description:BackgroundThe microbiome has been shown to affect the response to Immune Checkpoint Inhibitors (ICIs) in a small number of cancers and in preclinical models. Here, we sought to broadly survey cancers to identify those in which the microbiome may play a prognostic role using retrospective analyses of patients with advanced cancer treated with ICIs.MethodsWe conducted a retrospective analysis of 690 patients who received ICI therapy for advanced cancer. We used a literature review to define a causal model for the relationship between medications, the microbiome, and ICI response to guide the abstraction of electronic health records. Medications with precedent for changes to the microbiome included antibiotics, corticosteroids, proton pump inhibitors, histamine receptor blockers, non-steroid anti-inflammatories and statins. We tested the effect of medication timing on overall survival (OS) and evaluated the robustness of medication effects in each cancer. Finally, we compared the size of the effect observed for different classes of antibiotics to taxa that have been correlated to ICI response using a literature review of culture-based antibiotic susceptibilities.ResultsOf the medications assessed, only antibiotics and corticosteroids significantly associated with shorter OS. The hazard ratios (HRs) for antibiotics and corticosteroids were highest near the start of ICI treatment but remained significant when given prior to ICI. Antibiotics and corticosteroids remained significantly associated with OS even when controlling for multiple factors such as Eastern Cooperative Oncology Group performance status, Charlson Comorbidity Index score, and stage. When grouping antibiotics by class, β-lactams showed the strongest association with OS across all tested cancers.ConclusionsThe timing and strength of the correlations with antibiotics and corticosteroids after controlling for confounding factors are consistent with the microbiome involvement with the response to ICIs across several cancers.
| S-EPMC7201618 | biostudies-literature
Project description:Immune checkpoint inhibitors (ICIs) therapy is a novel strategy for cancer treatments in recent years. However, it was observed that most patients treated with ICIs could not get benefit from the therapy, which led to the limitation of clinical application. Motivated by potent and durable efficacy of ICIs, oncologists endeavor to explore the mechanisms of resistance to ICIs and increase the drug sensitivity. It is known that heterogeneity of gut microbiome in populations may result in different outcomes of therapy. In xenograft model, bacteria in gut have been proved as a crucial factor regulating immunotherapy efficacy. And the similar phenomenon was obtained in patients. In this review, we summarized relevant advancements about gut microbiome and ICIs. Furthermore, we focused on modulatory function of gut microbiome in ICIs therapy and possible antitumor mechanism of specific commensals in ICIs treatment. We propose that gut microbiome is an important predictive factor, and manipulation of gut microbiome is feasible to elevate response rate in ICIs therapy.
| S-EPMC5870075 | biostudies-literature
Project description: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.
| S-EPMC8578856 | biostudies-literature
Project description:Immune checkpoint inhibitors (ICIs) have been a major breakthrough in solid oncology over the past decade. The immune system and the gut microbiota are involved in their complex mechanisms of action. However, drug interactions have been suspected of disrupting the fine equilibrium necessary for optimal ICI efficacy. Thus, clinicians are facing a great deal of sometimes contradictory information on comedications with ICIs and must at times oppose conflicting objectives between oncological response and comorbidities or complications. We compiled in this review published data on the role of the microbiota in ICI efficacy and the impact of comedications. We found mostly concordant results on detrimental action of concurrent corticosteroids, antibiotics, and proton pump inhibitors. The timeframe seems to be an important variable each time to preserve an initial immune priming at ICIs initiation. Other molecules have been associated with improved or impaired ICIs outcomes in pre-clinical models with discordant conclusions in retrospective clinical studies. We gathered the results of the main studies concerning metformin, aspirin, and non-steroidal anti-inflammatory drugs, beta blockers, renin-angiotensin-aldosterone system inhibitors, opioids, and statins. In conclusion, one should always assess the necessity of concomitant treatment according to evidence-based recommendations and discuss the possibility of postponing ICI initiation or switching strategies to preserve the critical window.
| S-EPMC10136801 | biostudies-literature
Project description:Background and objectiveImmune checkpoint inhibitors (ICIs) have been widely applied and studied in the treatment of gastrointestinal (GI) cancers, and have achieved good results. However, in clinical practice, it has been observed that only some patients respond well to ICIs, and some patients may experience various degrees of adverse reactions during the treatment. Timely evaluation of the potential therapeutic effects and adverse reactions of ICIs for patients has important clinical significance. This review aimed to summarize recent progress regarding efficacy-associated biomarkers for ICIs in GI cancer.MethodsThe literature on ICI treatment in GI cancers was searched in the PubMed, Embase, and Cochrane Library databases for publications up to April 2023.Key content and findingsClinical practice and research has gradually revealed some biomarkers related to the treatment of GI cancers with ICIs, which can be roughly divided into three types: biomarkers that predict the effectiveness of ICIs treatment, biomarkers associated with resistance to ICIs, and biomarkers associated with immune related adverse events (irAEs). This review article provides a literature review on biomarkers related to the efficacy of ICIs in the treatment of GI cancers.ConclusionsAccording to existing clinical research results, there are multiple biomarkers that can be used for predicting and monitoring the efficacy and risk of adverse events of ICIs in the treatment of digestive system malignant tumors.
| S-EPMC10932650 | biostudies-literature
Project description:IntroductionImmune checkpoint inhibitors (ICI) is a rapidly evolving treatment modality for stage IV non-small cell lung cancer (NSCLC). Concomitant proton pump inhibitor (PPI) use can potentially reduce the clinical efficacy of ICIs; however, the consensus in recent literature has been conflicting. This study aims to analyze overall survival (OS) and progression-free survival (PFS) outcomes in patients with NSCLC on ICI and concomitant PPI therapy.MethodsA literature search was done in 3 databases (Pubmed/Medline, Embase, and Cochrane Central). All studies meeting the inclusion criteria assessing the impact of PPIs on the efficacy of ICI in NSCLC patients were systematically identified. A random-effects network meta-analysis evaluated OS and PFS in the two arms.ResultsFour studies with 2,940 patients are included in our analysis. ICI usage alone was associated with significantly better OS [HR = 1.46, 95% CI = 1.27-1.67, P < 0.00001] and PFS [HR = 1.31, 95% CI = 1.17-1.47, P < 0.00001] when compared to concomitant PPI and ICI therapy.ConclusionThe concomitant use of PPIs during ICI therapy significantly worsens clinical outcomes with shorter OS and increased risk of disease progression in patients with NSCLC.
| S-EPMC9119820 | biostudies-literature