What is the optimal duration of immune checkpoint inhibitors in malignant tumors?

Yin, Jiaxin; Song, Yanxing; Tang, Jiazhuo; Zhang, Bicheng

doi:10.3389/fimmu.2022.983581

Cited by 15 publications

(17 citation statements)

References 72 publications

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“…Furthermore, the optimal duration for IO treatment continues to be a topic of ongoing debate, several trials, including KEYNOTE-189 [ 24 ], KEYNOTE-010 [ 25 ], and CheckMate-153 [ 26 ], suggest the possibility of poor survival outcomes or disease progression after discontinuing IO treatment following one or two years of administration [ 27 ]. Limited research has managed to follow patients who discontinue treatment due to AEs.…”

Section: Discussionmentioning

confidence: 99%

Discontinuation risk from adverse events: immunotherapy alone vs. combined with chemotherapy: a systematic review and network meta-analysis

Shin,

Moon,

Oum

et al. 2024

BMC Cancer

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Background While immunotherapy combined with chemotherapy (Chemo-IO) is generally recognized for providing superior outcomes compared to monotherapy (mono-IO), it is associated with a higher incidence of treatment-related adverse events (TRAEs), which may lead to treatment discontinuation. In this study, we compared the rates of treatment discontinuation between mono-IO and Chemo-IO as first-line treatments for various solid tumors. Methods We systematically reviewed clinical trials from databases (PubMed, Embase, Cochrane Library, and an additional source) published from January 1, 2018, to July 10, 2023. We included phase III randomized controlled trials (RCTs) that utilized immunotherapy agents in at least one arm as first-line treatments for a variety of solid tumors. Data extraction followed the Preferred Reporting Items for Systematic Reviews (PRISMA) extension statement for network meta-analysis. A random effects model was used for the network meta-analysis, with the risk of bias assessed using the Cochrane risk-of-bias tool II. The primary outcomes encompassed treatment discontinuation rates due to TRAEs among patients who underwent immunotherapy, either alone or combined with chemotherapy, for various solid tumors. Pooled relative risks (RRs) with 95% confidence intervals (CIs) were calculated to compare between treatment groups. Results From 29 RCTs, a total of 21,677 patients and 5 types of treatment were analyzed. Compared to mono-IO, Chemo-IO showed a significantly higher rate of discontinuation due to TRAEs (RR 2.68, 95% CI 1.98–3.63). Subgroup analysis for non-small cell lung cancer (NSCLC) patients also exhibited a greater risk of discontinuation due to TRAEs with Chemo-IO compared to mono-IO (RR 2.93, 95% CI 1.67–5.14). Additional analyses evaluating discontinuation rates due to either treatment emergent adverse events (TEAEs) or AEs regardless of causality (any AEs) consistently revealed an elevated risk associated with Chemo-IO. Conclusions Chemo-IO was associated with an elevated risk of treatment discontinuation not only due to TRAEs but also any AEs or TEAEs. Given that the treatment duration can impact clinical outcomes, a subset of patients might benefit more from mono-IO than combination therapy. Further research is imperative to identify and characterize this subset.

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Section: Discussionmentioning

confidence: 99%

Discontinuation risk from adverse events: immunotherapy alone vs. combined with chemotherapy: a systematic review and network meta-analysis

Shin,

Moon,

Oum

et al. 2024

BMC Cancer

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“…To avoid selection bias, we enrolled patients consecutively, excluding those who had received less than two cycles of treatment. This subgroup represents a considerable proportion of patients with dismal prognoses, and their exclusion may have favorably influenced the evaluation of some correlations [ 52 ]. Furthermore, we were unable to ensure an independent reassessment of the radiology records, resulting in a potential overestimation of objective response rates.…”

Section: Discussionmentioning

confidence: 99%

Effects of Acetaminophen Exposure on Outcomes of Patients Receiving Immune Checkpoint Inhibitors for Advanced Non-Small-Cell Lung Cancer: A Propensity Score-Matched Analysis

Nelli,

Virtuoso,

Giannarelli

et al. 2023

Current Oncology

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(1) Background: Several studies have investigated potential interactions between immune checkpoint inhibitors (ICIs) and commonly prescribed medications. Although acetaminophen (APAP) has not been considered susceptible to interaction with ICIs, recent research has shown that detectable plasma levels of this drug can hinder the efficacy of PD-1/PD-L1 blockade therapies. A reliable assessment of the potential interaction between APAP and ICIs in advanced non-small cell lung cancer (NSCLC) patients would be worthwhile since it is often prescribed in this condition. We sought to evaluate the impact of the concomitant use of APAP in patients with advanced NSCLC on PD-1/PD-L1 blockade using real-world evidence. (2) Methods: This study included consecutive patients with histologically proven stage IV NSCLC who underwent first-line therapy with pembrolizumab as a single agent or in combination with platinum-based chemotherapy, or second-line therapy with pembrolizumab, nivolumab, or atezolizumab. The intensity of APAP exposure was classified as low (therapeutic intake lasting less than 24 h or a cumulative intake lower than 60 doses of 1000 mg) or high (therapeutic intake lasting more than 24 h or a total intake exceeding 60 doses of 1000 mg). The favorable outcome of anti-PD-1/PD-L1 therapies was defined by durable clinical benefit (DCB). Progression-free survival (PFS) and overall survival (OS) were relevant to our efficacy analysis. Propensity score matching (PSM) methods were applied to adjust for differences between the APAP exposure subgroups. (3) Results: Over the course of April 2018 to October 2022, 80 patients were treated with first-line pembrolizumab either as single-agent therapy or in combination with platinum-based chemotherapy. During the period from June 2015 to November 2022, 145 patients were given anti-PD-1/PD-L1 blockade therapy as second-line treatment. Subsequent efficacy analyses relied on adjusted PSM populations in both treatment settings. Multivariate testing revealed that only the level of APAP and corticosteroid intake had an independent effect on DCB in both treatment lines. Multivariate Cox regression analysis confirmed high exposure to APAP and immunosuppressive corticosteroid therapy as independent predictors of shorter PFS and OS in both treatment settings. (4) Conclusions: Our findings would strengthen the available evidence that concomitant intake of APAP blunts the efficacy of ICIs in patients with advanced NSCLC. The detrimental effects appear to depend on the cumulative dose and duration of exposure to APAP. The inherent shortcomings of the current research warrant confirmation in larger independent series.

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“…A previous study suggested that the similarity of real-world data to their clinical trial analogues depended on the drug class [ 28 ]. In this study, ICIs may have had prolonged effectiveness after stopping the treatment [ 29 ]; therefore, the PFS might have been longer than the end of treatment in the claims database. EGFR-TKIs are often used beyond progressive disease in patients with NSCLC [ 30 ], and the PFS may therefore be shorter than the DoT.…”

Section: Discussionmentioning

confidence: 99%

Real-World Data About Treatment Outcomes for Patients with EGFR-Mutated NSCLC Resistance to Osimertinib and Platinum-Based Chemotherapy

Hayashi¹,

Nishio²,

Takahashi³

et al. 2023

Adv Ther

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Introduction Docetaxel is an established standard therapy after osimertinib and platinum-based doublet chemotherapy (Pt-doublet) for locally advanced or metastatic non-small cell lung cancer (NSCLC) with an epidermal growth factor receptor gene ( EGFR ) mutation. To facilitate future therapeutic developments in these patients after treatment with osimertinib and Pt-doublet, we estimated the outcomes of currently used post-treatment therapies. Methods Data of patients with NSCLC who received at least one medication after osimertinib and Pt-doublet between April 2008 and August 2021 were extracted from the Medical Data Vision claims database. The duration of treatment (DoT) (first treatment after osimertinib and Pt-doublet) and overall survival (OS) were estimated. The index date was the first day on which the medication was prescribed. Results In total, 731 patients (mean age 64 years) were screened. The most frequent post-treatments were docetaxel-based chemotherapy (30.2%), immune checkpoint inhibitor (ICI) alone or in combination (17.2%), first-/second-generation EGFR-tyrosine kinase inhibitors (16.7%), osimertinib (16.3%), and Pt-doublet (5.2%). The median DoT and OS (95% confidence interval) of all post-treatments were 3.5 (3.27, 3.77) and 10.3 (9.3, 12.1) months, respectively, reflecting the median DoT (3.8 months) and OS (10.0 months) of docetaxel-based chemotherapy. Among all post-treatment regimens, ICIs resulted numerically the shortest [2.77 (2.33, 3.00) months] and osimertinib the longest [4.40 (3.47, 5.67) months] median DoT. The median OS was shortest in patients post-treated with ICIs [7.07 (5.40, 9.90) months] and longest in patients rechallenged with Pt-doublet (12.27 months), followed by patients post-treated with osimertinib (11.70 months). In a subset analysis of patients who received first-line osimertinib and second-line Pt-doublet as well as Pt-doublet immediately after osimertinib, those post-treated with ICIs had the shortest median DoT. Conclusion Given the limited real-world efficacy on EGFR -mutant NSCLC resistant to osimertinib and platinum-based chemotherapy, the development of more highly potent post-treatment therapies is warranted.

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What is the optimal duration of immune checkpoint inhibitors in malignant tumors?

Cited by 15 publications

References 72 publications

Discontinuation risk from adverse events: immunotherapy alone vs. combined with chemotherapy: a systematic review and network meta-analysis

Discontinuation risk from adverse events: immunotherapy alone vs. combined with chemotherapy: a systematic review and network meta-analysis

Effects of Acetaminophen Exposure on Outcomes of Patients Receiving Immune Checkpoint Inhibitors for Advanced Non-Small-Cell Lung Cancer: A Propensity Score-Matched Analysis

Real-World Data About Treatment Outcomes for Patients with EGFR-Mutated NSCLC Resistance to Osimertinib and Platinum-Based Chemotherapy

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