Secondary spontaneous pneumothorax in patients with sarcoma treated with Pazopanib, a case control study

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.

Pneumothorax as an Adverse Event in Patients with Lung Metastasis of Soft Tissue Sarcoma under Eribulin Treatment

“…In addition, Nakano et al found that risk factors for pneumothorax in patients with STS lung metastases during pazopanib treatment were lung metastases with a ≥30-mm maximum diameter and the presence of a history of pneumothorax before pazopanib treatment (6). In contrast, a recent case control study suggested that pazopanib did not increase the risk of pneumothorax in patients with lung metastases from STS (8). However, that study had several limitations, one being that the odds of developing pneumothorax in patients with STS on pazopanib were retrospectively analyzed using a purposeful selection method.…”

Anti-Angiogenic Agents in Management of Sarcoma Patients: Overview of Published Trials

“…Sabath et al. have identified pre-treatment cavitation (odds ratio [OR] = 7.0, p<0.001) and pleural or base location of lung nodules (OR = 10.4, p<0.001) as independent risk factors ( 77 ). Nakano et al.…”

Secondary pneumothorax as a potential marker of apatinib efficacy in osteosarcoma: a multicenter analysis

“…Nonetheless, the exact reasons for the discrepancy are unknown. Pazopanib is another multitarget TKI that has a high probability of causing pneumothorax in patients with sarcomas [8,17,18]; the targets of pazopanib are also different from those of apatinib (Table 3) [19]. Different targets result in different effectiveness of the two TKIs for osteosarcoma treatment.…”

“…These TKIs inhibit a variety of tyrosine kinases, and although their multitarget nature has led to effective treatment of osteosarcoma, it has also caused various adverse events. A growing number of studies have shown that pneumothorax is one of adverse events (AEs) associated with treatment of sarcomas using multitarget TKIs [5,8,9].…”