Atezolizumab for Pretreated Non-Small Cell Lung Cancer with Idiopathic Interstitial Pneumonia: Final Analysis of Phase II AMBITIOUS Study

Ikeda, Satoshi; Kato, Terufumi; Kenmotsu, Hirotsugu; Ogura, Takashi; Sato, Yuki; Hino, Aoi; Harada, Toshiyuki; Kubota, Keiichi; Tokito, Takaaki; Okamoto, Isamu; Furuya, Naoki; Yokoyama, Toshihide; Hosokawa, Shinobu; Iwasawa, Tae; Kasajima, Rika; Miyagi, Yohei; Misumi, Toshihiro; Okamoto, Hiroaki

doi:10.1093/oncolo/oyac118

Cited by 13 publications

(10 citation statements)

References 12 publications

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“…37/50 studies were considered to have low risk of bias for prognostic factor measurement, with clear information on data source and data handling ( Table 2 ). 13/50 studies were evaluated to have high risk of bias due to unclear description on the source of the prognostic factors (2/13, Table 3 ) ( 33 , 55 ), use of data-driven discretization that was optimized to maximise discrimination (5/13, Table 3 ) ( 11 , 39 , 44 , 53 , 58 ), and lack of information on data processing such as the handling of missing data or discretization (5/13, Table 3 ) ( 11 , 19 , 21 , 39 , 64 ). Additionally, 5/13 studies simply excluded subjects with missing data from the analysis when the proportion of missing values were high (> 10% missing, Table 3 ) ( 32 , 40 , 53 – 55 ).…”

Section: Resultsmentioning

confidence: 99%

Common methodological pitfalls in ICI pneumonitis risk prediction studies

Chen,

Welsh,

Pillay

et al. 2023

Front. Immunol.

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BackgroundPneumonitis is one of the most common adverse events induced by the use of immune checkpoint inhibitors (ICI), accounting for a 20% of all ICI-associated deaths. Despite numerous efforts to identify risk factors and develop predictive models, there is no clinically deployed risk prediction model for patient risk stratification or for guiding subsequent monitoring. We believe this is due to systemic suboptimal approaches in study designs and methodologies in the literature. The nature and prevalence of different methodological approaches has not been thoroughly examined in prior systematic reviews.MethodsThe PubMed, medRxiv and bioRxiv databases were used to identify studies that aimed at risk factor discovery and/or risk prediction model development for ICI-induced pneumonitis (ICI pneumonitis). Studies were then analysed to identify common methodological pitfalls and their contribution to the risk of bias, assessed using the QUIPS and PROBAST tools.ResultsThere were 51 manuscripts eligible for the review, with Japan-based studies over-represented, being nearly half (24/51) of all papers considered. Only 2/51 studies had a low risk of bias overall. Common bias-inducing practices included unclear diagnostic method or potential misdiagnosis, lack of multiple testing correction, the use of univariate analysis for selecting features for multivariable analysis, discretization of continuous variables, and inappropriate handling of missing values. Results from the risk model development studies were also likely to have been overoptimistic due to lack of holdout sets.ConclusionsStudies with low risk of bias in their methodology are lacking in the existing literature. High-quality risk factor identification and risk model development studies are urgently required by the community to give the best chance of them progressing into a clinically deployable risk prediction model. Recommendations and alternative approaches for reducing the risk of bias were also discussed to guide future studies.

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Section: Resultsmentioning

confidence: 99%

Common methodological pitfalls in ICI pneumonitis risk prediction studies

Chen,

Welsh,

Pillay

et al. 2023

Front. Immunol.

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“…The identification of risk factors for serious ICIP is warranted. I keda et al [ 23 ]. reported that a honeycomb lung on HRCT may be a risk factor for ICIP through a logistic regression analysis.…”

Section: Discussionmentioning

confidence: 99%

“…Thus, prospective studies of second-line or later ICI therapy for lung cancer with mild IP suggests high efficacy. The TORG1936/AMBITIOUS trial of atezolizumab in previously treated patients with NSCLC with IP was discontinued due to frequent episodes of ICIP; the ICIP incidence was 29.4% (n=5) for all grades, 23.5% (n=4) for grade 3 or higher and 6% (n=1) for grade 5 [ 22 , 23 ]. Therefore, the safety of immunotherapy for patients with IP and lung cancer remains unknown.…”

Section: Introductionmentioning

confidence: 99%

Immune checkpoint inhibitors in patients with lung cancer having chronic interstitial pneumonia

Isobe,

Nakamura,

Sakamoto

et al. 2024

ERJ Open Res

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BackgroundIn interstitial pneumonia (IP)-associated lung cancer, immune checkpoint inhibitor pneumonitis (ICIP) is common with immune checkpoint inhibitor (ICI) treatment.PurposeTo clarify the safety and efficacy of ICI for lung cancer with IP.MethodsThis multicentre retrospective observational study was conducted from June 2016 to December 2020 on patients with primary lung cancer with IP who received ICI.ResultsA total of 200 patients (median age 70 years; male/female, 176/24) were enrolled from 27 institutions. ICIP occurred in 61 patients (30.5%), grades 3–5 pneumonitis in 32 patients (15.5%) and death in nine patients (4.5%). The common computed tomography (CT) pattern of ICIP was organising pneumonia in 29 patients (47.5%). Subsequently, diffuse alveolar damage (DAD) pattern was observed in 19 patients (31.1%) who had a significantly worse prognosis than those with a non-DAD pattern (median progression-free survival [PFS]: 115 daysversus226 days p=0.042; median overall survival [OS]: 334 daysversus1316 days, p<0.001). Immune-related adverse events (irAE) occurred in approximately 50% of patients. Patients with irAEs (n=100) had a better prognosis than those without irAEs (n=100) (median PFS: 200 daysversus77 days, p<0.001; median OS: 597 daysversus390 days p=0.0074). The objective response rate and disease control rate were 41.3% and 68.5%, respectively.ConclusionsAlthough ICI treatment was effective for lung cancer with IP, ICIP developed in approximately 30%. Patients with irAE had a significantly better PFS and OS than those without irAE.

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“…docetaxel and pemetrexed) as second-line or later therapy in NSCLC patients with comorbid interstitial pneumonia showed a 1-year survival of, at most, 10%, which is far from promising for long-term survival [ 6 , 7 ]. Conversely, phase II trials of ICIs for NSCLC patients with interstitial pneumonia have consistently shown favourable efficacy; a nivolumab trial had a median overall survival of 15.6 months, while an atezolizumab trial had a 1-year survival rate of 53.3% [ 4 , 8 ]. Since ICIs are the only treatment option that can provide long-term survival in poor-prognosis lung cancer patients with interstitial pneumonia, an important clinical issue is how to “narrow down” interstitial pneumonias with low risk of ICI-induced pneumonitis.…”

mentioning

confidence: 99%