Pleural effusion is a negative prognostic factor for immunotherapy in patients with non-small cell lung cancer (NSCLC): The pluie study

Epaillard, Nicolas; Benítez, José Carlos; Gorría, Teresa; Fabre, Elizabeth; Riudavets, Mariona; Reyes, Roxana; Planchard, David; Oudard, Stéphane; Viñolas, Núria; Reguart, Noemı́; Besse, Benjamin; Mezquita, Laura; Auclin, Édouard

doi:10.1016/j.lungcan.2021.03.015

Cited by 14 publications

(22 citation statements)

References 19 publications

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“…23 24 In a multicentre retrospective series, patients with metastatic non-small cell lung cancer and pleural effusion treated with anti-PD(L)-1 agents showed poorer survival outcomes and higher early death rates, even in the subgroup with high PD-L1 expression. 25 Our work has several potential implications for clinical practice. First, a subset of patients may sometimes develop ascites as a late-stage complication of peritoneal metastases.…”

Section: Open Accessmentioning

confidence: 93%

Ascites and resistance to immune checkpoint inhibition in dMMR/MSI-H metastatic colorectal and gastric cancers

Fucà

Cohen

Lonardi

et al. 2022

J Immunother Cancer

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BackgroundDespite unprecedented benefit from immune checkpoint inhibitors (ICIs) in patients with mismatch repair deficient (dMMR)/microsatellite instability high (MSI-H) advanced gastrointestinal cancers, a relevant proportion of patients shows primary resistance or short-term disease control. Since malignant effusions represent an immune-suppressed niche, we investigated whether peritoneal involvement with or without ascites is a poor prognostic factor in patients with dMMR/MSI-H metastatic colorectal cancer (mCRC) and gastric cancer (mGC) receiving ICIs.MethodsWe conducted a global multicohort study at Tertiary Cancer Centers and collected clinic-pathological data from a cohort of patients with dMMR/MSI-H mCRC treated with anti-PD-(L)1 ±anti-CTLA-4 agents at 12 institutions (developing set). A cohort of patients with dMMR/MSI-high mGC treated with anti-PD-1 agents±chemotherapy at five institutions was used as validating dataset.ResultsThe mCRC cohort included 502 patients. After a median follow-up of 31.2 months, patients without peritoneal metastases and those with peritoneal metastases and no ascites had similar outcomes (adjusted HR (aHR) 1.15, 95% CI 0.85 to 1.56 for progression-free survival (PFS); aHR 0.96, 95% CI 0.65 to 1.42 for overall survival (OS)), whereas inferior outcomes were observed in patients with peritoneal metastases and ascites (aHR 2.90, 95% CI 1.70 to 4.94; aHR 3.33, 95% CI 1.88 to 5.91) compared with patients without peritoneal involvement. The mGC cohort included 59 patients. After a median follow-up of 17.4 months, inferior PFS and OS were reported in patients with peritoneal metastases and ascites (aHR 3.83, 95% CI 1.68 to 8.72; aHR 3.44, 95% CI 1.39 to 8.53, respectively), but not in patients with only peritoneal metastases (aHR 1.87, 95% CI 0.64 to 5.46; aHR 2.15, 95% CI 0.64 to 7.27) when compared with patients without peritoneal involvement.ConclusionsPatients with dMMR/MSI-H gastrointestinal cancers with peritoneal metastases and ascites should be considered as a peculiar subgroup with highly unfavorable outcomes to current ICI-based therapies. Novel strategies to target the immune-suppressive niche in malignant effusions should be investigated, as well as next-generation ICIs or intraperitoneal approaches.

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Section: Open Accessmentioning

confidence: 93%

Ascites and resistance to immune checkpoint inhibition in dMMR/MSI-H metastatic colorectal and gastric cancers

Fucà

Cohen

Lonardi

et al. 2022

J Immunother Cancer

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“…In line with our data, the authors observed that pleural involvement as composite variable together with malignant pleural effusion both combined were associated with poor outcomes, which could be explained by the fact that pleural cavity is a natural permeable barrier that can limit the penetration of cancer therapies. 32 With regard to the influence of bone metastasis on survival, most attention has been given to skeletal-related events (SREs), which impair quality of life and are understood to affect survival directly or indirectly. 33 In the present study, we did not observe specific effect of bone metastasis on PFS, which may indicate that EGFR-TKIs are effective and well tolerated in responders.…”

Section: Discussionmentioning

confidence: 99%

Establishment of prognostic nomograms for predicting the progression free survival of EGFR‐sensitizing mutation, advanced lung cancer patients treated with EGFR‐TKIs

Bai

Wang

et al. 2022

Thoracic Cancer

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Background There is a lack of clinically available predictive models for patients with epidermal growth factor receptor (EGFR) mutation positive, advanced non–small cell lung cancer (NSCLC) treated with EGFR‐tyrosine kinase inhibitors (TKIs). Methods The clinical data of patients at the Cancer Hospital, Chinese Academy of Medical Sciences between from January 2016 to January 2021 were retrospectively retrieved as training set. The patients from BENEFIT trial were for the validation cohort. The nomogram was built based on independent predictors identified by univariate and multivariate Cox regression analyses. The discrimination and calibration of the nomogram were evaluated by C‐index and calibration plots. Results A total of 502 patients with complete clinical data and follow‐up information were enrolled in this study. Five independent prognostic factors, including The Eastern Cooperative Oncology Group Performance Status scale (ECOG PS), EGFR mutation subtype, EGFR co‐mutation, liver metastasis and malignant pleural effusion (p < 0.05). The C‐indexes of the nomogram were 0.694 (95% confidence interval [CI], 0.663–0.725) for the training set and 0.653 (95% CI, 0.610–0.696) for the validation set. The calibration curves for the probabilities of 9‐, 12‐ and 18‐month progression‐free survival (PFS) revealed satisfactory consistency in both the internal and external validations. Additionally, the patients were divided into two groups according to risk (high‐risk, low‐risk), and significant differences in PFS were observed between the groups in the training and external validation cohorts (p < 0.001). Conclusions We constructed and validated a convenient nomogram that have the potential to become an accurate and reliable tool for patients with EGFR mutation positive, advanced NSCLC to individually predict their potential benefits from EGFR‐TKIs, and facilitate clinical decision‐making.

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“…However, growing pieces of evidence are emerging about a negative prognostic role of metastatic pleural site. Recently, pleural effusion was an independent negative prognostic factor in NSCLC patients receiving ICI or ICI combinations in different treatment lines, with one-third of patients with pleural effusion experiencing early death [8].…”

Section: Discussionmentioning

confidence: 99%

“…In particular, within the high PD-L1 range, it could be useful to assess the value of PD-L1 as a prognostic marker together with clinical features based on recent evidence [23]. Moreover, recent retrospective studies identified the negative prognostic role of high neutrophil to lymphocyte ratio (NLR, with different cut-offs), as well as albumin and lactate dehydrogenase in blood, and included it into prognostic models in addition to clinical features including ECOG PS, steroid use, metastatic sites in patients receiving ICIs [8,24,25]. However, biomarker assessment was not included in our study, as it was designed to specifically evaluate clinical features that are routinely used in clinical practice for patient evaluation and treatment selection.…”

Section: Discussionmentioning

confidence: 99%

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Early Progression in Non-Small Cell Lung Cancer (NSCLC) with High PD-L1 Treated with Pembrolizumab in First-Line Setting: A Prognostic Scoring System Based on Clinical Features

Passaro

Novello

Giannarelli

et al. 2021

Cancers

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Background: Pembrolizumab is approved in monotherapy for the first-line (1L) of advanced or metastatic NSCLC patients with high PD-L1 (≥50%). Despite a proportion of patients achieve long-term survival, about one-third of patients experience detrimental survival outcomes, including early death, hyperprogression, and fast progression. The impact of clinical factors on early progression (EP) development has not been widely explored. Methods: We designed a retrospective, multicenter study involving five Italian centers, in patients with metastatic NSCLC with PD-L1 ≥ 50%, treated with Pembrolizumab in a 1L setting. EP was defined as a progressive disease within three months from pembrolizumab initiation. Baseline clinical factors of patients with and without EP were collected and analyzed. Logistic regression was performed to identify clinical factors associated with EP and an EP prognostic score was developed based on the logistic model. Results: Overall, 321 out of 336 NSCLC patients treated with 1L pembrolizumab provided all the data for the analysis. EP occurred in 137 (42.7%) patients; the median PFS was 3.8 months (95% CI: 2.9–4.7), and median OS was not reached in the entire study population. Sex, Eastern Cooperative Oncology Group (ECOG) performance status (PS), steroids, metastatic sites ≥2, and the presence of liver/pleural metastasis were confirmed as independent factors for EP by multivariate analysis. By combining these factors, we developed an EP prognostic score ranging from 0–13, with three-risk group stratification: 0–2 (good prognosis), 3–6 (intermediate prognosis), and 7–13 (poor prognosis). The area under the curve (AUC) of the model was 0.76 (95% CI: 0.70–0.81). Conclusions: We identified six clinical factors independently associated with EP. We developed a prognostic score model for EP-risk to potentially improve clinical practice and patient selection for 1L pembrolizumab in NSCLC with high PD-L1, in the real-world clinical setting.

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Pleural effusion is a negative prognostic factor for immunotherapy in patients with non-small cell lung cancer (NSCLC): The pluie study

Cited by 14 publications

References 19 publications

Ascites and resistance to immune checkpoint inhibition in dMMR/MSI-H metastatic colorectal and gastric cancers

Ascites and resistance to immune checkpoint inhibition in dMMR/MSI-H metastatic colorectal and gastric cancers

Establishment of prognostic nomograms for predicting the progression free survival of EGFR‐sensitizing mutation, advanced lung cancer patients treated with EGFR‐TKIs

Early Progression in Non-Small Cell Lung Cancer (NSCLC) with High PD-L1 Treated with Pembrolizumab in First-Line Setting: A Prognostic Scoring System Based on Clinical Features

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