Malignant pleural effusion as a predictor of the efficacy of anti‐PD‐1 antibody in patients with non‐small cell lung cancer

Abstract

Background The aim of this study was to evaluate the usefulness of the presence of malignant pleural effusion (MPE) as a negative predictor of anti‐PD‐1 antibody efficacy. Methods A retrospective review of patients with advanced or recurrent non‐small cell lung cancer treated with an anti‐PD‐1 antibody between December 2015 and March 2018 at the National Cancer Center Hospital, Japan, was conducted. Progression‐free survival (PFS) and overall survival (OS) were compared between patients with and without MPE. Additional survival analysis according to PD‐L1 expression status was conducted. Univariate and multivariate analyses were performed. Results A total of 252 patients were identified before the commencement of anti‐PD‐1 antibody treatment: 33 with MPE and 219 without MPE. PFS and OS were significantly shorter in patients with MPE than in patients without MPE (median PFS 3.0 vs. 5.8 months, hazard ratio [HR] 1.7, P = 0.014; median OS 7.9 vs. 15.8 months, HR 2.1, P = 0.001). In patients with PD‐L1 expression in ≥ 1% of their tumor cells, the PFS of patients with MPE was significantly shorter than of patients without MPE (median PFS 3.1 vs. 6.5 months, HR 2.0, 95% confidence interval 1.0–3.5; P = 0.021). The presence of MPE was independently associated with a shorter PFS and OS in multivariate analysis. Conclusion The presence of MPE in patients administered an anti‐PD‐1 antibody is associated with shorter PFS and OS, regardless of the presence of PD‐L1 expression ≥ 1% of tumor cells.

Radiographic features and poor prognostic factors of interstitial lung disease with nivolumab for non–small cell lung cancer

“…Recently, malignant pleural effusion has been associated with shorter progression-free survival and overall survival in NSCLC patients treated with anti-PD-1 antibodies. [19][20][21] Taken together, the presence of pleural effusion before treatment may be one of the noteworthy factors when considering nivolumab as a therapeutic candidate for NSCLC. The identification of abnormal change in CRP levels as a poor prognostic factor may be related to its role as a marker of inflammation.…”

Prediction of patients with a tumor proportion score >50% who do not respond to first-line monotherapy with pembrolizumab

“…The results showed that the response rate was markedly lower in patients with pleural or pericardial metastasis than that observed in those without pleural or pericardial metastasis [11]. Shibaki et al reported that the presence of malignant pleural effusion was an independent negative predictor affecting PFS and OS, regardless of the presence of positive PD-L1 expression [12].…”

“…Furthermore, these studies showed that ICI monotherapy tended to be less effective in patients with pleural effusion. However, the mechanism responsible for the low efficacy of ICIs observed in patients with pleural effusion remains to be elucidated [11,12].…”

Prediction of patients with a tumor proportion score > 50% who do not respond to first-line monotherapy with pembrolizumab

“…The results showed that the response rate was markedly lower in patients with pleural or pericardial metastasis than that observed in those without pleural or pericardial metastasis [11]. Shibaki et al reported that the presence of malignant pleural effusion was an independent negative predictor affecting PFS and OS, regardless of the presence of positive PD-L1 expression [12]. Furthermore, these studies showed that ICI monotherapy tended to be less effective in patients with pleural effusion.…”

“…Furthermore, these studies showed that ICI monotherapy tended to be less effective in patients with pleural effusion. However, the mechanism responsible for the low efficacy of ICIs observed in patients with pleural effusion remains to be elucidated [11,12]. The KEYNOTE-189 study investigated patients with previously untreated metastatic non-squamous NSCLC without epidermal growth factor receptor or anaplastic lymphoma kinase mutations.…”