Second-line chemotherapy in malignant pleural mesothelioma: results of a retrospective multicenter survey

Our plain-English summary of Second-line chemotherapy in malignant pleural mesothelioma: results of a retrospective multicenter survey, by P.A. Zucali, M. Simonelli, G. Michetti, et al (Lung Cancer, 2012).

The study

• Authors: P.A. Zucali, M. Simonelli, G. Michetti, M. Tiseo, G.L. Ceresoli, E. Collovà, A. Follador, M. Lo Dico, A. Moretti, F. De Vincenzo, E. Lorenzi, M. Perrino, L. Giordano, G. Farina, A. Santoro, M. Garassino
• Journal: Lung Cancer
• Published: 2012;75(3):360-7
• Cited by: 66 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

The pemetrexed-cisplatin chemotherapy is standard of care in first-line (FL) treatment of malignant pleural mesothelioma (MPM). The second-line (SL) chemotherapy is considered, but the optimal treatment has not been defined yet. The aim of this study was to evaluate the clinical outcomes of SL-therapy in a series of MPM-patients included in a retrospective multicenter database. Clinical records of MPM-patients who received SL-treatment from 1996 to 2008 were reviewed. Study endpoints were response, overall-survival (OS), and progression-free-survival (PFS) for SL, stratified for patient characteristics, FL-outcomes, and type of SL. Out of 423 patients, 181 with full clinical data were identified. Patients' characteristics: median-age 64 years (range: 36-85); male gender 115 (63.5%); good EORTC-score 109 (60.2%); epithelial histology 135 (74.6%). After FL, 147 (81.2%) patients achieved disease-control (DC) and 45 had a time-to-progression≥12 months (TTP≥12). After SL, 95 patients (52.6%) achieved DC (21 response; 74 stable-disease); median PFS and OS were 4.3 and 8.7 months, respectively. According to multivariate analysis, DC after SL-therapy was significantly related to pemetrexed-based treatment (OR: 2.46; p=0.017) and FL-TTP≥12 (OR: 3.50; p=0.006). PFS was related to younger age (<65 years) (HR: 0.70; p=0.045), ECOG-PS0 (HR: 0.67; p=0.022), and FL-TTP≥12 (HR: 0.45; p<0.001). OS was significantly related to ECOG-PS0 (HR: 0.43; p<0.001) and to FL-TTP≥12 (HR: 0.54; p=0.005). In pemetrexed pre-treated patients, re-treatment with a pemetrexed/platinum combination significantly reduced the risk-of-death than pemetrexed alone (HR: 0.11; p<0.001). In conclusion, SL-chemotherapy seems to be active in MPM-patients, particularly in younger patients with ECOG-PS0 and prolonged TTP after FL-pemetrexed-based chemotherapy. In selected patients, re-challenge with pemetrexed-based regimens, preferentially associated with platinum-compound, appears to be an option for SL-setting. Considering the important limitations of this study, due to retrospective nature and the possible selection bias, prospective clinical trials are warranted to clarify these issues.

Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

In plain English

This study examined second-line chemotherapy (after first treatment failed) for malignant pleural mesothelioma. It did not study asbestos exposure. The authors reviewed records of 423 such patients at eight Italian institutions, 1996 to 2008. They analysed the 181 (43%) with full clinical data. Overall, 52.6% had disease control; median progression-free survival was 4.3 months and median overall survival 8.7 months. Longer progression-free and overall survival were associated with performance status ECOG 0 and a first-line time to progression of 12 months or more. Among 120 patients first treated with pemetrexed, the 42 given pemetrexed again lived longer than those given other drugs (10.6 versus 7.0 months). In the multivariate analysis, however, pemetrexed-containing therapy was not confirmed as an independent factor for overall survival. Within the 42, pemetrexed plus a platinum drug (31 patients) was linked to longer survival than pemetrexed alone (11 patients): adjusted hazard ratio for death 0.11 (95% CI 0.04 to 0.30). The authors noted possible selection bias and small subgroups. They concluded pemetrexed/platinum re-treatment seemed better than pemetrexed alone and called for prospective trials.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Retrospective multicenter review of patient records (survey of second-line treatments given outside clinical trials)
• Who was studied: Patients with malignant pleural mesothelioma treated with second-line chemotherapy at eight Italian centers, 1996 to 2008. Of 423 such patients, 181 had full clinical data and were analysed: median age 64, 115 male, 135 with epithelial histology.
• Exposure: No asbestos exposure was studied. The 'exposure' was second-line chemotherapy: pemetrexed-based regimens (with or without cisplatin or carboplatin) and other regimens (for example vinorelbine, gemcitabine, platinum combinations, biological agents).
• Main results:
  • Whole group (181): disease control rate 52.6%. This was 1 complete response, 20 partial responses and 74 with stable disease.
  • Whole group: median progression-free survival 4.3 months, at a median follow-up of 43.3 months.
  • Whole group: median overall survival 8.7 months. Estimated survival was 34.3% at 1 year and 15.3% at 2 years.
  • Whole group, multivariate analysis: disease control was associated with second-line pemetrexed-based treatment (OR 2.46, 95% CI 1.18 to 5.14) and with first-line time to progression of 12 months or more (OR 3.50, 95% CI 1.4 to 8.6).
  • Whole group, multivariate analysis: two factors were associated with reduced risk of both progression and death. These were ECOG performance status 0 (progression HR 0.67, 95% CI 0.47 to 0.94; death HR 0.43) and first-line time to progression of 12 months or more (progression HR 0.45, 95% CI 0.29 to 0.69; death HR 0.54, 95% CI 0.35 to 0.83). Age under 65 was associated with reduced risk of progression (HR 0.70, 95% CI 0.50 to 0.99).
  • Pemetrexed-naive patients (61): there was no significant difference in progression-free or overall survival between those given pemetrexed-based and non-pemetrexed second-line treatment.
  • Pemetrexed-pretreated patients: the 42 re-challenged with pemetrexed were compared with the 78 given a non-pemetrexed second-line regimen. Disease control rate was 70.7% versus 52.0%. Progression-free survival was 6.2 versus 2.8 months. Overall survival was 10.6 versus 7.0 months.
  • In the multivariate analysis for overall survival in pemetrexed-pretreated patients, pemetrexed-containing second-line therapy was not confirmed as an independent factor.
  • Among the 42 re-treated with pemetrexed, the 31 given pemetrexed plus a platinum compound were compared with the 11 given pemetrexed alone. Progression-free survival was 6.4 versus 2.4 months. Overall survival was 13.4 versus 4.2 months.
  • In the same 42 pemetrexed re-treated patients, multivariate analysis linked pemetrexed combined with platinum to a reduced risk of death (HR 0.11, 95% CI 0.04 to 0.30).
  • The 52 patients re-treated with platinum-based second-line chemotherapy were compared with the 116 given second-line chemotherapy without platinum. Disease control rate was 70.6% versus 44.6%. Progression-free survival was 6.6 versus 2.5 months. Overall survival was 11.6 versus 6.3 months.
• The authors' conclusion: The authors concluded that re-treatment with a pemetrexed-containing regimen should be considered in selected patients who had a prolonged response to first-line pemetrexed-based chemotherapy. They also concluded that pemetrexed/platinum re-treatment seems better than pemetrexed alone, and that prospective trials are needed.
• Limitations the authors state:
  • Retrospective design.
  • Possible selection bias: patients who receive second-line therapy tend to be fitter and to have benefited from earlier treatment.
  • Fewer than half of the reviewed patients had full data and were included.
  • Subgroups were not truly independent and were small, which reduced statistical power.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Mesothelioma.

Medical terms in this study, explained in our Lexicon: Chemotherapy, Pleural Mesothelioma, Pemetrexed (Alimta), Cisplatin, Histology, Multivariate Analysis, Selection Bias, Clinical Trial.

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