A retrospective analysis of second-line chemotherapy for malignant pleural mesothelioma (MPM).

Abstract

7040 Background: Chemotherapy is the only option for MPM. Cisplatin + pemetrexed became the standard in the first-line (FL), while the role of a second-line (SL) remains controversial. Methods: We retrospectively collected data of all consecutive MPM patients (pts), from 8 italian institutions, receiving SL chemotherapy after a platinum based FL treatment from 1996 to 2008. The primary endpoint was overall survival (OS). Secondary endpoints were progression-free survival (PFS), best overall response rate (ORR) and prognostic factors. Kaplan Meier curves and Log Rank were used for statistical analysis. Results: Of 414 MPM pts treated in FL setting, 161 underwent a SL chemotherapy (63% male; median age 62.5 years). Main regimens were: platinum rechallenge (21 pts, 13.1%), pemetrexed rechallenge: (23 pts - 14.4%), pemetrexed + platinum rechallenge (32 pts-20%), biological agents (23 pts-14.3%) and others (62 pts-38.2%). 89 pts achieved disease control (partial remission + stable disease) with a SL regimen (55,6%) (median OS 10,23 months (mths), median PFS 5.72 mths). OS was statistically significantly higher in pts rechallenged with platinum + pemetrexed (20.56 vs 8.49 mths – HR 0.39 95%IC 0.21-0.71; p = 0.0015), while PFS wasn't (9.77 vs 5.39 mths – HR 0.71 95%IC 0.47-1.08; p = 0.111). PFS (p < 0.0001) and OS (p < 0.0001) were statistically significant in pts responding to FL and with an epithelial histology (p = 0.0008). Univariate and multivariate logistic analysis showed that the only factors for the choice of SL regimen were response after FL and smokers. Conclusions: The benefit of SL is strictly dependent on histology and response to FL. According to our data, rechallenge with platinum-based regimens seems the best option. No benefit has been proven in favour of polichemotherapy regimens in respect to single agents. The superiority of cisplatin + pemetrexed rechallenge has been demonstrated also at the multivariate analysis adjusted for time to SL and histology. The role of platinum-based rechallenge in SL should be further investigated, considering also that a SL has palliative intent on the basis of histology and of the extent of response to FL treatment. No significant financial relationships to disclose.