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Pleural Effusion Emerges as a Negative Prognostic Factor for Immune Checkpoint Inhibitor Treatment in Patients with Non-Small Cell Lung Cancer

Pleural effusion was associated with worse patient characteristics, poorer survival and higher early death rates
09 Dec 2020
Cancer Immunology and Immunotherapy;  Lung and other thoracic tumours

Patients with non-small cell lung cancer (NSCLC) and pleural effusion (PE), especially those requiring pleural evacuation, experienced poorer survival when treated with immune checkpoint inhibitors (ICIs) according to findings presented at the ESMO Immuno-Oncology Virtual Congress 2020, held from 9 to 12 December 2020.

Nicolas Epaillard of the Oncology, Hopital Européen Georges Pompidou in Paris, France and colleagues explained that the pleura is a common site of metastatic involvement in patients with NSCLC and the pleura also acts as a natural barrier that can limit the penetration and efficacy of ICI, which led to the PLUIE study assessment of the clinical outcome of PE in patients with NSCLC who were treated with an ICI.

This multicentre international retrospective study identified 538 patients with NSCLC who were treated with an ICI from November 2012 to November 2019. The investigators stratified this cohort by PE (n=196) versus non-PE (n=342) as of the immunotherapy baseline.

Overall survival (OS) and the early death rate served as the primary endpoints while the secondary outcomes were progression-free survival (PFS) and the disease control rate (DCR). The association between outcomes and PE was evaluated using logistic regression, whereas univariate and multivariate Cox models were performed for OS and PFS.

The median patient age in the overall population was 62.9 years, 34.6% of patients were female, 9.5% were never smokers, and 75.7% of patients had non-squamous NSCLC. The characteristics were similar in the PE group: the patients’ median age was 64.4 years, 31.6% were female, 12.4% were never smokers, and 77.6% had non-squamous NSCLC. ICI was administered as first- or second-line in 66% of patients and 94% of patients received the ICI as monotherapy.

In terms of patient characteristics, an association was found between PE and a higher number of metastatic sites: the PE cohort had a median of 3.5 metastatic sites compared to a median 2.7 metastatic sites in the non-PE cohort. PE also associated with poorer ECOG performance status (PS): 90.8% of PE patients versus 80.5% of non-PE patients had PS ≥2.  

Overall survival was significantly shorter in PE patients compared to non-PE patients

Regarding the primary objective, the overall cohort demonstrated median OS of 9.7 months (95% confidence interval [CI] 8.1-11.8), whereas the PE cohort had a median OS of 6.3 months (95% CI 4.0-8.6) compared to 11.4 months (95% CI 9.7-13.8) in the non-PE cohort (p = 0.002). The early death rate was 31.4% in the overall cohort, while the early death rates in the PE compared to non-PE cohorts were 38.3% versus 27.5% (odds ratio [OR] 1.63; 95% CI 1.13-2.37; p = 0.01). 

Pleural-Effusion-Emerges-as-a-Negative-Prognostic-Factor-for-Immune-Checkpoint-Inhibitor-Treatment-in-Patients-with-Non-Small-Cell-Lung-Cancer

Response endpoints according to the presence of pleural effusion.

© Nicolas Epaillard.

PFS, a secondary endpoint, was 1.8 months (95% CI 1.7-2.5) in the PE cohort compared to 2.3 months (95% CI 2.0-3.6) in the non-PE group (p = 0.04).

PE was a consistent independent prognostic factor for survival across adjusted analyses

Following adjustment for PS, liver, intracranial, or bone metastasis, the immunotherapy line, and the derived neutrophil to lymphocyte ratio (dNLR), PE remained an independent prognostic factor for OS (hazard ratio [HR] 1.38; 95% CI 1.09-1.74; p = 0.007) and PFS (HR 1.35, 95% CI 1.09-1.68; p = 0.006).

The DCR was 49.9% in the PE compared to 52.3% in non-PE patients (OR 1.64; 95% CI 1.14-2.40, p = 0.01).

Of the 196 patients in the PE cohort, 73 (37.2%) patients required pleural evacuation, which was associated with a significantly increased early death rate of 52% in pleural evacuated patients versus 30.5% in non-evacuated patients (p = 0.003).

Conclusions

The authors concluded that pleural effusion is associated with worse prognosis and lower responses to treatment with an immune checkpoint inhibitor.

No external funding was disclosed.

Reference

42P – Epaillard N, Benitez JC, Gorria T, et al. Pleural effusion is a negative prognostic factor for immunotherapy in non-small cell lung cancer (NSCLC): The PLUIE study. ESMO Immuno-Oncology Virtual Congress 2020 (9-12 December).

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