ABSTRACT
Malignant pleural mesothelioma (MPM) is a rare pleural cancer associated with asbestos exposure. According to current evidence, the combination of chemotherapy, surgery and radiotherapy improves patients' survival. However, the optimal sequence and weighting of the respective treatment modalities is unclear. In anticipation of the upcoming results of the MARS-2 trial, we sought to determine the relative impact of the respective treatment modalities on complications and overall survival in our own consecutive institutional series of 112 patients. Fifty-seven patients (51%) underwent multimodality therapy with curative intent, while 55 patients (49%) were treated with palliative intent. The median overall survival (OS) of the entire cohort was 16.9 months (95% CI: 13.4−20.4) after diagnosis; 5-year survival was 29% for patients who underwent lung-preserving surgery. In univariate analysis, surgical treatment (p < 0.001), multimodality therapy (p < 0.001), epithelioid subtype (p < 0.001), early tumor stage (p = 0.02) and the absence of arterial hypertension (p = 0.034) were found to be prognostic factors for OS. In multivariate analysis, epithelioid subtype was associated with a survival benefit, whereas the occurrence of complications was associated with worse OS. Multimodality therapy including surgery significantly prolonged the OS of MPM patients compared with multimodal therapy without surgery.
ABSTRACT
The second-generation ALK tyrosine kinase inhibitor brigatinib has recently been approved in the European Union for use after crizotinib treatment in patients with EML4-ALK-rearranged lung cancer. In the current study, brigatinib was investigated as second-line or later-line treatment in 35 patients who had developed resistance to crizotinib, ceritinib, or alectinib. Most patients (68.6%) received brigatinib as second or third line (range: second to 12th line). In the total cohort, complete and partial responses were obtained for 9.1 and 75.8%, respectively. Overall median progression-free survival was 9.9 months, whereas the largest treatment cohort (brigatinib after crizotinib failure) showed a median progression-free survival of 8.4 months. Fifty-four percent of patients with baseline brain metastases responded to brigatinib treatment. Brigatinib was highly effective after crizotinib and ceritinib failure. Six patients had received alectinib as monotherapy, second-line, or third line before brigatinib; of these, four experienced partial responses and two progressed responses. Brigatinib treatment was well tolerated.
