Combination use of paclitaxel and avastin enhances treatment effect for the NSCLC patients with malignant pleural effusion

e21660 Background: Prospective and retrospective studies on intrapleural therapy of malignant pleural effusion (MPE) have reported that the success rate for controlling pleural effusion was 50–70% at 2.5 months, and that the median post-pleurodesis survival time was 6-9 months. When pleurodesis is unsuccessful, and the lung is not fully expanded after drainage, the patients cannot receive effective chemotherapy. Vascular endothelial growth factor (VEGF) plays a pivotal role in the pathogenesis of MPE. Here, a multicenter phase II trial was conducted to evaluate bevacizumab therapy in non-squamous non-small cell lung carcinoma patients with unsuccessful management of MPE. Methods: Non-squamous NSCLC patients with MPE who had received unsuccessful tube drainage or pleurodesis received chemotherapy with bevacizumab (15 mg/kg) every 3 weeks. The primary endpoint was Pleural effusion control rate (PECR), defined as the percentage of patients without reaccumulation of MPE for 8 weeks. The secondary endpoint was pleural Progression-free survival (PPFS), defined as PFS without reaccumulation of MPE. Results: Fifteen of 20 patients entered received a median of 4 cycles of carboplatin plus paclitaxel or pemetrexed including maintenance therapy with bevacizumab. The PECR was 80% of treated patients (95% CI: 78-82%). PPFS was 16.6 months (95% CI: 11.46-21.80 months). The response rate (RR) and disease control rate (DCR) were 45% (95% CI: 39.6-50.4%), and 80% (95% CI: 78.0-82.0 %), respectively, and the median PFS and overall survival (OS) were 9.8 months (95% CI: 4.38-15.28 months) and 19.6 months (95% CI: 4.38-15.28 months), respectively. Toxicities of grade ≥3 included neutropenia (50.0%), thrombocytopenia (10.0%), proteinuria (10.0%), hypertension (2.0%), pulmonary embolism (5%). Conclusions: The combination of bevacizumab with chemotherapy demonstrated efficacy with acceptable toxicities in controlling MPE in patients with non-squamous NSCLC whose MPE was unsuccessfully controlled by tube drainage or pleurodesis.

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The relationship between metastatic sites and progression free survival of nivolumab in non-small cell lung cancer patients.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.e20679 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. e20679-e20679 ◽

Cited By ~ 1

Author(s):

Motohiro Tamiya ◽

Akihiro Tamiya ◽

Hidekazu Suzuki ◽

Takako Inoue ◽

Yoshihiko Taniguchi ◽

...

Keyword(s):

Lung Cancer ◽

Liver Metastasis ◽

Pleural Effusion ◽

Malignant Pleural Effusion ◽

Progression Free Survival ◽

Small Cell ◽

Small Cell Lung ◽

Free Survival ◽

Metastatic Sites ◽

Nsclc Patients

e20679 Background: Nivolumab (Nivo) is applicable for all metastatic or unresectable non-small cell lung cancer (NSCLC), however only some patients benefit from it. Therefore, identifying biomarkers predicting efficacy is a crucial topic in the “real world’’ setting. We conducted a retrospective study to analyze the impact of metastatic status on the effect of Nivo in NSCLC patients. Methods: This is a retrospective multicenter study conducted by the three medical centers in Japan. All patients treated with Nivo from January 2016 to July 2016 in these centers were retrospectively reviewed. We collected clinical data including age, sex, smoking history, performance status (PS), and metastatic cites (lymph nodes: lym, liver, brain, bone, pleural effusion, and intrapulmonary metastasis: lung) at the time of starting Nivo treatment. We investigated relationship between metastatic sites and progression free survival (PFS) of Nivo. Patients were followed-up until 30th September 2016. Results: Two hundred and one patients treated with Nivo were enrolled. At the time of administration of Nivo, median age was 68 years old, 137 patients were male, 155 patients had history of smoking status, 152 patients were PS 0 or 1, and 46 patients had squamous cell carcinoma (SQ). For all participants, median PFS was 2.5 months. In univariate analysis, female (hazard ratio (HR): 1.43, 95% confidence interval (CI): 1.02-2.00; p = 0.036), never-smoker (HR: 1.51 , 95% CI: 1.05 – 2.17; p = 0. 0262), PS 2 or more (HR: 1.68, 95% CI: 1.17-2.41; p = 0.0045), metastasis to liver (HR: 2.02, 95% CI: 1.30-3.15; p = 0.0015), brain (HR: 1.42, 95% CI: 0.99-2.03; p = 0.0574), bone (HR: 1.42, 95% CI: 1.01-1.98; p = 0.0642), lung (HR: 1.57, 95% CI: 1.13-2.20; p = 0.0076), and malignant pleural effusion (HR: 1.47, 95% CI: 1.06-2.04; p = 0.0195) had significantly correlated with poor PFS. In multivariate analysis, liver metastasis (HR: 1.59, 95% CI: 0.97-2.61; p = 0.0642) and malignant pleural effusion (HR: 1.47, 95%CI: 1.04–2.07; p = 0.0294) had significantly correlated with poor PFS. Conclusions: Liver metastasis and malignant pleural effusion were independent poor prognostic factors of Nivo treatment in NSCLC patients. (UMIN-ID: UMIN000025908)

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Addition of bevacizumab for malignant pleural effusion as the manifestation of acquired EGFR-TKI resistance in NSCLC patients

Oncotarget ◽

10.18632/oncotarget.16061 ◽

2017 ◽

Vol 8 (37) ◽

pp. 62648-62657 ◽

Cited By ~ 6

Author(s):

Tao Jiang ◽

Aiwu Li ◽

Chunxia Su ◽

Xuefei Li ◽

Chao Zhao ◽

...

Keyword(s):

Pleural Effusion ◽

Malignant Pleural Effusion ◽

Tki Resistance ◽

Nsclc Patients ◽

Egfr Tki

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Intrapleural Injection of Anti-PD1 Antibody: A Novel Management of Malignant Pleural Effusion

Frontiers in Immunology ◽

10.3389/fimmu.2021.760683 ◽

2021 ◽

Vol 12 ◽

Author(s):

Xinying Li ◽

Guannan Wu ◽

Cen Chen ◽

Yuan Zhao ◽

Suhua Zhu ◽

...

Keyword(s):

T Cells ◽

Pleural Effusion ◽

Cd8 T Cells ◽

Malignant Pleural Effusion ◽

Malignant Tumors ◽

Cytotoxic T Cells ◽

Lymphocyte Activation ◽

Local Injection ◽

And Function ◽

Nsclc Patients

BackgroundMalignant tumors accompanied with malignant pleural effusion (MPE) often indicate poor prognosis. The therapeutic effect and mechanism of intrapleural injection of anti-programmed cell death protein 1 (PD1) on MPE need to be explored.MethodsA preclinical MPE mouse model and a small clinical study were used to evaluate the effect of intrapleural injection of anti-PD1 antibody. The role of immune cells was observed via flow cytometry, RNA-sequencing, quantitative PCR, western blot, immunohistochemistry, and other experimental methods.ResultsIntrathoracic injection of anti-PD1 monoclonal antibody (mAb) has significantly prolonged the survival time of mice (P = 0.0098) and reduced the amount of effusion (P = 0.003) and the number of cancer nodules (P = 0.0043). Local CD8+ T cells participated in intrapleural administration of anti-PD1 mAb. The proportion of CD69+, IFN-γ+, and granzyme B+ CD8+ T cells in the pleural cavity was increased, and the expression of TNF-α and IL-1β in MPE also developed significantly after injection. Local injection promoted activation of the CCL20/CCR6 pathway in the tumor microenvironment and further elevated the expression of several molecules related to lymphocyte activation. Clinically, the control rate of intrathoracic injection of sintilimab (a human anti-PD1 mAb) for 10 weeks in NSCLC patients with MPE was 66.7%. Local injection improved the activity and function of patients’ local cytotoxic T cells (CTLs).ConclusionsIntrapleural injection of anti-PD1 mAb could control malignant pleural effusion and the growth of cancer, which may be achieved by enhancing local CTL activity and cytotoxicity.

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