Vinorelbine as second or third-line therapy in pemetrexed-pretreated malignant pleural mesothelioma (MPM) patients

Background: There is no standard therapy for patients (pts) with MPM progressing during or after pemetrexed/platinum-based chemotherapy (PBC). Single agent chemotherapy is often administered in everyday practice, although its use is poorly supported by clinical trials. The aim of this retrospective study was to analyze the efficacy and toxicity of second (2nd) and third (3rd) line vinorelbine (VNR) in a large cohort of PBC-pretreated MPM patients.Methods: The clinical records of MPM pts consecutively treated at 8 Italian Centers with intravenous (iv) or oral (po) VNR as 2nd or 3rd line therapy following PBC were reviewed. Radiological response was assessed by modified RECIST criteria. Toxicity was reported according to CTCAEv4 criteria. Relative dose-intensity (DI) of VNR was calculated. Progression-free survival (PFS) and overall survival (OS) were estimated and correlated to clinical variables: age, gender, histological subtype, ECOG performance status (PS), line of VNR therapy (2nd vs 3rd) and outcome of first-line treatment.Results: From August 2001 to September 2014, 161 pts (M/F 120/41) were treated, 128 with iv and 33 with po VNR. Most cases (92%) were treated after 2007. Histological subtype was epithelioid in 134, biphasic in 15, sarcomatoid in 8 and unspecified in 4 pts. Median age was 67 years (range 41-82). VNR was administered as 2nd or 3rd line treatment in 94 and 67 pts, respectively. Median number of VNR cycles was 3 (range 1-26), median relative DI was 88%. Main grade 3-4 toxicities were neutropenia in 9%, fatigue in 4% and constipation in 5% of pts. No toxic death occurred. A partial response was observed in 10 pts (6%), stable disease in 57 (35%), for an overall disease control rate of 41%. Median PFS and OS were 2.5 and 6.7 months, respectively. In multivariate analysis, only ECOG PS (0 vs 1-2) was significantly associated with improved PFS and OS. Median PFS and OS in pts with ECOG PS 0 were 3.3 and 8.5 months. An analysis of molecular predictors of VNR response is ongoing.Conclusions: In this large retrospective patient cohort, 2nd and 3rd line VNR had modest but definite activity in PBC-pretreated MPM patients, with a good toxicity profile. Although inclusion in prospective clinical trials of new agents should be always considered in this setting, single agent VNR remains a reasonable option for palliation. Background: There is no standard therapy for patients (pts) with MPM progressing during or after pemetrexed/platinum-based chemotherapy (PBC). Single agent chemotherapy is often administered in everyday practice, although its use is poorly supported by clinical trials. The aim of this retrospective study was to analyze the efficacy and toxicity of second (2nd) and third (3rd) line vinorelbine (VNR) in a large cohort of PBC-pretreated MPM patients. Methods: The clinical records of MPM pts consecutively treated at 8 Italian Centers with intravenous (iv) or oral (po) VNR as 2nd or 3rd line therapy following PBC were reviewed. Radiological response was assessed by modified RECIST criteria. Toxicity was reported according to CTCAEv4 criteria. Relative dose-intensity (DI) of VNR was calculated. Progression-free survival (PFS) and overall survival (OS) were estimated and correlated to clinical variables: age, gender, histological subtype, ECOG performance status (PS), line of VNR therapy (2nd vs 3rd) and outcome of first-line treatment. Results: From August 2001 to September 2014, 161 pts (M/F 120/41) were treated, 128 with iv and 33 with po VNR. Most cases (92%) were treated after 2007. Histological subtype was epithelioid in 134, biphasic in 15, sarcomatoid in 8 and unspecified in 4 pts. Median age was 67 years (range 41-82). VNR was administered as 2nd or 3rd line treatment in 94 and 67 pts, respectively. Median number of VNR cycles was 3 (range 1-26), median relative DI was 88%. Main grade 3-4 toxicities were neutropenia in 9%, fatigue in 4% and constipation in 5% of pts. No toxic death occurred. A partial response was observed in 10 pts (6%), stable disease in 57 (35%), for an overall disease control rate of 41%. Median PFS and OS were 2.5 and 6.7 months, respectively. In multivariate analysis, only ECOG PS (0 vs 1-2) was significantly associated with improved PFS and OS. Median PFS and OS in pts with ECOG PS 0 were 3.3 and 8.5 months. An analysis of molecular predictors of VNR response is ongoing. Conclusions: In this large retrospective patient cohort, 2nd and 3rd line VNR had modest but definite activity in PBC-pretreated MPM patients, with a good toxicity profile. Although inclusion in prospective clinical trials of new agents should be always considered in this setting, single agent VNR remains a reasonable option for palliation.