Abstract
BackgroundThe tyrosine kinase inhibitor pazopanib is used for treatment of sarcoma. Recent studies have suggested that the use of pazopanib may lead to the development of pneumothorax, an unexpected adverse effect in patients with sarcoma metastatic to the chest.MethodsWe conducted a retrospective case control study of patients with sarcoma with metastases to the chest with pneumothorax (cases) and without pneumothorax (controls). The control population was selected from tumor registry in a 1:4 (cases to controls) ratio. The primary outcome of interest was the association between pazopanib and pneumothorax risk in patients with sarcoma metastatic to the chest. Secondary objective was to evaluate risk factors for pneumothorax.ResultsWe identified 41 cases and 164 controls. Using purposeful selection method the odds of developing pneumothorax while being on pazopanib was not significant in univariate (p = .06) and multivariable analysis (p = .342). On univariate analysis risk factors of pneumothorax in patients with sarcoma were age, male sex, African American race, the presence of cavitary lung nodules/masses, and the presence of pleural-based nodules/masses. On multivariate analysis, only the presence of cavitary lung nodules/masses (P < .001) and the presence of pleural-based nodules/masses (P < .001) remained as risk factors for developing pneumothorax.ConclusionPazopanib does not increase the risk of pneumothorax in patients with sarcoma and evidence of metastatic disease to the chest. Presence of cavitary lung nodules/masses and the presence of pleural-based nodules/masses were found to be risk factors for pneumothorax.
Highlights
The tyrosine kinase inhibitor pazopanib is used for treatment of sarcoma
To determine whether pazopanib is associated with spontaneous pneumothorax (SSP) in patients with sarcoma we used purposeful selection variables in logistic regression [18]. We used this method to improve the chances of retaining meaningful confounders, and we looked at the association of the exposure variable with the other covariates and only included those variables that are associated with the exposure of interest [18]
The remaining 117 patients presented with a secondary spontaneous pneumothorax associated with metastatic disease to the chest, among whom 41 had sarcoma
Summary
The tyrosine kinase inhibitor pazopanib is used for treatment of sarcoma. Recent studies have suggested that the use of pazopanib may lead to the development of pneumothorax, an unexpected adverse effect in patients with sarcoma metastatic to the chest. Several studies have reported an association between metastatic osteogenic or soft tissue sarcomas with pneumothorax, especially in the setting of cytotoxic chemotherapy or radiotherapy [1, 2]. A multitarget tyrosine kinase inhibitor, was approved in 2012 for the treatment of soft tissue sarcoma on the basis of evidence of improved progression-free survival in advanced disease [13]. Since the introduction of pazopanib, pneumothorax has been reported as an unexpected adverse event. Other studies of pazopanib prescribed for non-sarcoma cancers did not report pneumothorax as an adverse event [15,16,17]. Higher quality evidence is needed to investigate the question on whether pazopanib is truly a risk factor
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