Pazopanib or placebo in completely resected stage I NSCLC patients: results of the phase II IFCT-0703 trial

Besse, Benjamin; Mazières, Julien; Ribassin-Majed, Laureen; Barlési, Fabrice; Bennouna, Jaafar; Gervais, Radj; Moreau, L.; Bérard, H.; Debieuvre, D.; Molinier, Olivier; Moro-Sibilot, Denis; Souquet, Pierre-Jean; Jacquot, S.; Petit, L.; Léna, H.; Pignon, Jean-Pierre; Lacas, Benjamin; Morin, Franck; Milleron, B.; Zalcman, Gérard; Soria, Jean‐Charles

doi:10.1093/annonc/mdx070

Cited by 17 publications

(4 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…After reading the titles and abstracts, 168 studies were obtained. After reading the full text, 34 RCTs ( Richardson et al, 2018 ; Zhao et al, 2021b ; Motzer et al, 2013a ; Motzer et al, 2013b ; Sternberg et al, 2013 ; Rini et al, 2011 ; Kudo et al, 2018 ; Yang et al, 2017 ; Vilgrain et al, 2017 ; Spreafico et al, 2014 ; Sun et al, 2018 ; Symonds et al, 2015 ; Thornton et al, 2012 ; Qin et al, 2021 ; Schoffski et al, 2021 ; Sheng et al, 2019 ; Belani et al, 2014 ; Besse et al, 2017 ; Blay et al, 2020 ; Bukowski et al, 2007 ; Chi et al, 2021 ; Choueiri et al, 2020 ; Ellis et al, 2014 ; du Bois et al, 2014 ; Martin et al, 2017 ; Gravalos et al, 2018 ; Gross-Goupil et al, 2018 ; Zhou et al, 2019 ; Hall et al, 2020 ; Haas et al, 2021 ; Machiels et al, 2018 ; Langerbeins et al, 2015 ; Li et al, 2016 ; Schlumberger et al, 2015 ) were finally included ( Figure 2 ).…”

Section: Resultsmentioning

confidence: 99%

Renal adverse reactions of tyrosine kinase inhibitors in the treatment of tumours: A Bayesian network meta-analysis

et al. 2022

View full text Add to dashboard Cite

Objectives: Tumours remain a serious threat to human life. Following rapid progress in oncology research, tyrosine kinase inhibitors have been used to treat multiple tumour types. Given the great influence of kidneys on pharmacokinetics, renal toxicities associated with TKIs have attracted attention. However, the TKIs with the lowest risks of renal impairment are unclear. In this study, we conducted a Bayesian network meta-analysis to compare the incidence of renal impairment among different TKIs in patients with tumours.Methods and analysis: Six databases (PubMed, EMBASE, The Cochrane Library, Chinese National Knowledge Infrastructure, Wanfang Data, and China Biomedical Literature Database) were electronically searched from inception to 1 November 2021 to identify randomized controlled trials on the incidence of renal impairment for different TKIs in patients with tumours. Two reviewers independently screened the literature, extracted data, and assessed the risk of bias of the included studies. Then, a pairwise meta-analysis was conducted using Stata version 13, and network meta-analysis within the Bayesian framework was conducted using R software version 3.5.3 with the package “gemtc 0.8–2” recalling JAGS (version 4.3.0).Results: Overall, 34 randomized controlled trials were included in this study. Although renal toxicity was common among patients receiving TKIs, the incidence and severity greatly differed among the drugs and studies. Elevated creatinine and protein levels were the most common nephrotoxic events, whereas haematuria was relatively rare. Among TKIs, nintedanib and ripretinib carried the lowest risks of renal impairment.Conclusion: TKIs displayed different profiles of renal toxicity because of their different targets and underlying mechanisms. Clinicians should be aware of the risks of renal impairment to select the optimal treatment and improve patient adherence to treatment.Systematic Review Registration: [www.crd.york.ac.uk/prospero/], identifier [CRD42022295853].

show abstract

Section: Resultsmentioning

confidence: 99%

Renal adverse reactions of tyrosine kinase inhibitors in the treatment of tumours: A Bayesian network meta-analysis

et al. 2022

View full text Add to dashboard Cite

show abstract

“…Since the main objective of this systematic review was to focus on the methodology of seamless phase II/III design, we categorized the 28 eligible trials into 4 distinct categories: (a) Phase II/III trials with inefficacy/futility analyses [ 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 ], (b) Dose escalation Phase II/III trials [ 31 , 32 , 33 , 34 , 35 ], (c) Multi-Arm Multi Stage (MAMS) phase II/III trials [ 36 ], (d) Trials with other design [ 37 , 38 , 39 , 40 , 41 ].…”

Section: Resultsmentioning

confidence: 99%

“…Two other trials shared the same design, in which the phase II and phase III primary endpoints were feasibility/compliance and DFS (disease-free survival), respectively. Feasibility/compliance was defined as adherence to a specific regimen for a prespecified time period, by means of self-reporting or pill counting [ 37 , 38 ]. The last trial [ 39 ] reported a design in which patients stayed on trial even after disease progression, to capture and evaluate the possible chemo-sensitization effects seen in previous trials with the same investigational medicinal product.…”

Section: Resultsmentioning

confidence: 99%

Lung Cancer Clinical Trials with a Seamless Phase II/III Design: Systematic Review

Palermos

Sergentanis

Gavriatopoulou

et al. 2022

JCM

View full text Add to dashboard Cite

Current lung cancer clinical research focuses on biomarkers and personalized treatment strategies. Adaptive clinical trial designs have gained significant ground due to their increased flexibility, compared to the conventional model of drug development from phase I to phase IV trials. One such adaptive approach is the seamless phase II/III design, which has been used to reduce the total sample size and drug development time. In this context, an algorithmic systematic search was conducted in MEDLINE (PUBMED), SCOPUS, EMBASE and Cochrane Central Register of Controlled Trials until 31 June 2022 in order to identify lung cancer trials of systematic treatments that have employed the seamless phase II/III methodology and to describe their characteristics. The search strategy yielded a total of 1420 records that were screened through their title and abstract; 28 eligible trials were included in the systematic review. Based on the study endpoints, the most common subtype included phase II/III trials with inefficacy/futility analyses (61%; 17/28), followed by dose escalation phase II/III trials (18%; 5/28), one multi-arm multi stage trial and 5 trials with other design (18%). Most eligible trials were open-label (71%; 20/27), included patients with non-small cell lung cancer (82%; 23/28), evaluated targeted therapies and/or immunotherapies (82%; 23/28) and recruited patients with advanced disease (89.3%; 25/28). In conclusion, the seamless phase II/III design is a feasible and suitable approach in lung cancer research, with distinct design subcategories according to study endpoints.

show abstract

“…For the moment, there are no data on its efficacy. Pazopanib, an oral anti-angiogenic drug used as adjuvant therapy in resected stage I patients failed to improve relapse-free survival [28]. In this context, ICIs, which can induce both cell-mediated immunity against proliferating cancer cells following complete resection and establish immunological memory that may guard against future recurrences through active immune surveillance are a particularly attractive therapeutic option [29], especially as early-stage disease may have fewer mechanisms of resistance to ICIs.…”

Section: Immune-related Adverse Events a New Category Of Drug Toxicitymentioning

confidence: 99%

Immunotherapy: a new standard of care in thoracic malignancies?

et al. 2018

View full text Add to dashboard Cite

In May 2017, the second European Respiratory Society research seminar of the Thoracic Oncology Assembly entitled "Immunotherapy, a new standard of care in thoracic malignancies?" was held in Paris, France. This seminar provided an opportunity to review the basis of antitumour immunity and to explain how immune checkpoint inhibitors (ICIs) work. The main therapeutic trials that have resulted in marketing authorisations for use of ICIs in lung cancer were reported. A particular focus was on the toxicity of these new molecules in relation to their immune-related adverse events. The need for biological selection, currently based on immunohistochemistry testing to identify the tumour expression of programmed death ligand (PD-L)1, was stressed, as well as the need to harmonise PD-L1 testing and techniques. Finally, sessions were dedicated to the combination of ICIs and radiotherapy and the place of ICIs in nonsmall cell lung cancer with oncogenic addictions. Finally, an important presentation was dedicated to the future of antitumour vaccination and of all ongoing trials in thoracic oncology.

show abstract

Pazopanib or placebo in completely resected stage I NSCLC patients: results of the phase II IFCT-0703 trial

Abstract: In resected stage I NSCLC patients adjuvant 400 mg/day pazopanib but not 800 mg/day was feasible, although possibly infra-therapeutic and failed to improve relapse-free survival.

Cited by 17 publications

References 18 publications

Renal adverse reactions of tyrosine kinase inhibitors in the treatment of tumours: A Bayesian network meta-analysis

Renal adverse reactions of tyrosine kinase inhibitors in the treatment of tumours: A Bayesian network meta-analysis

Lung Cancer Clinical Trials with a Seamless Phase II/III Design: Systematic Review

Immunotherapy: a new standard of care in thoracic malignancies?

Contact Info

Product

Resources

About