Retreatment with pemetrexed-based chemotherapy in patients with malignant pleural mesothelioma

Our plain-English summary of Retreatment with pemetrexed-based chemotherapy in patients with malignant pleural mesothelioma, by G.L. Ceresoli, P.A. Zucali, F. De Vincenzo, et al (Lung Cancer, 2011).

The study

• Authors: G.L. Ceresoli, P.A. Zucali, F. De Vincenzo, L. Gianoncelli, M. Simonelli, E. Lorenzi, C. Ripa, L. Giordano, A. Santoro
• Journal: Lung Cancer
• Published: 2011;72(1):73-7
• Cited by: 95 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

The role of second-line therapy in patients with malignant pleural mesothelioma (MPM) progressing after first-line pemetrexed-based chemotherapy (PBC) is currently undefined. Recent case series have suggested a possible role of re-treatment with PBC. In this observational study, the activity and safety of this therapeutic option was assessed in a consecutive series of cases. Patients with complete response (CR), partial response (PR) or stable disease (SD) lasting for at least 3 months after first-line PBC were retreated with PBC, either as second-line (2L) or further-line (>2L) therapy. Descriptive analyses of progression-free survival (PFS), overall survival (OS), response rate and toxicity are reported. Between October 2004 and July 2009, 31 patients (21 males and 10 females) received re-treatment with PBC as 2L (18 patients) or beyond 2L therapy (13 patients). Median age was 65 years (range 37-81). Fifteen patients were re-treated with pemetrexed alone, and 16 with a pemetrexed/platinum combination. An objective response was achieved in 6 patients (one CR and 5 PRs), for a response rate of 19%. Nine patients (29%) had SD after treatment. Overall, the disease control rate (DCR) was 48%. Median PFS and overall survival (OS) after re-treatment with PBC were 3.8 months and 10.5 months, respectively. PFS and OS after re-treatment with PBC were correlated with PFS achieved after first-line PBC (FL-PFS). Patients with a FL-PFS >12 months had a median PFS after re-treatment of 5.5 months, while patients with a FL-PFS ≤12 months had a median PFS after re-treatment of 2.5 months; no patient in this group was progression-free at 1 year. Toxicity was mild, with grade 3 or 4 hematological toxicity occurring in 9.7% of patients. In conclusion, re-treatment with PBC should be considered as second-line therapy in MPM patients achieving a durable (>12 months) disease control with first-line PBC. Further prospective evaluation of this therapeutic option is warranted.

Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

In plain English

This observational study at two linked Italian centers examined giving pemetrexed-based chemotherapy again to people with malignant pleural mesothelioma whose disease had been controlled for at least 3 months by first-line pemetrexed-based chemotherapy. Between October 2004 and July 2009, 31 patients (21 men, 10 women; median age 65) were re-treated, 15 with pemetrexed alone and 16 with pemetrexed plus a platinum drug. One patient had a complete response and 5 a partial response (response rate 19%); the disease control rate was 48%. Median progression-free survival was 3.8 months and median overall survival 10.5 months. Patients whose first-line progression-free survival exceeded 12 months had a median progression-free survival after re-treatment of 5.5 months, against 2.5 months for those at 12 months or less (p = 0.004). One-year overall survival in these two groups was 71.0% versus 18.8% (p = 0.077). Grade 3 or 4 blood toxicity occurred in 3 patients (9.7%). The authors concluded re-treatment seems a viable option in selected patients with first-line progression-free survival longer than 12 months, and noted the small number of patients and an obvious selection bias.

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: Observational study of a consecutive series of patients (descriptive analysis, no statistical design)
• Who was studied: 31 patients with malignant pleural mesothelioma (21 males, 10 females; median age 65, range 37 to 81) treated at two Italian institutions between October 2004 and July 2009. They were drawn from 122 patients who progressed after first-line pemetrexed-based chemotherapy. 32 were re-treated, and one was excluded from the analysis.
• Exposure: Re-treatment with pemetrexed-based chemotherapy: 15 patients received pemetrexed alone and 16 received a pemetrexed/platinum combination (14 with carboplatin, 1 with carboplatin and bevacizumab, 1 with cisplatin). 18 received it as second-line therapy and 13 beyond second line. Asbestos exposure was not addressed.
• Main results:
  • Among all 31 patients, 1 had a complete response and 5 had a partial response, an objective response rate of 19%.
  • Among all 31 patients, 9 (29%) had stable disease and 16 (52%) had progressive disease. The disease control rate was 48%.
  • Responses occurred only in patients with epithelial histotype who received re-treatment as second-line therapy.
  • For the whole group, median progression-free survival was 3.8 months (range 1.2 to 17.7 months) and the 1-year progression-free survival estimate was 8%.
  • For the whole group, median overall survival was 10.5 months (range 2.0 to 34.2 months).
  • Patients re-treated as second-line therapy had longer median progression-free survival than those re-treated beyond second line (p less than 0.001). Overall survival was also longer for the second-line group (p = 0.027).
  • Patients whose progression-free survival after first-line treatment was longer than 12 months had a median progression-free survival after re-treatment of 5.5 months and a 1-year progression-free survival of 16.7%. Those whose first-line progression-free survival was 12 months or less had a median of 2.5 months, and none was progression-free at 1 year (p = 0.004).
  • One-year overall survival was 71.0% in patients with first-line progression-free survival longer than 12 months and 18.8% in those with 12 months or less (p = 0.077).
  • Grade 3 or 4 hematological (blood) toxicity occurred in 3 of 31 patients (9.7%), including one case of febrile neutropenia.
• The authors' conclusion: The authors concluded that, in selected cases with progression-free survival longer than 12 months, re-treatment with pemetrexed-based chemotherapy seems to be a viable option. They added that only a prospective randomized evaluation and better patient selection will further define its role.
• Limitations the authors state:
  • The authors cited the study design and the relatively low number of patients included.
  • The authors noted obvious selection bias: re-treated patients were a selected group in good general condition who had benefited for a long time from previous treatments.

Topics

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

Medical terms in this study, explained in our Lexicon: Pemetrexed (Alimta), Chemotherapy, Pleural Mesothelioma, Second-Line Therapy, Progression-Free Survival, Overall Survival.

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• Pemetrexed in malignant pleural mesothelioma and the clinical outcome — A. Knuuttila, E.R. Salomaa, et al. (2012)
• Second-line treatment for malignant pleural mesothelioma — G.L. Ceresoli, P.A. Zucali, et al. (2010)
• Molecular resistance fingerprint of pemetrexed and platinum in a long-term survivor of mesothelioma — O.D. Røe, A. Szulkin, et al. (2012)
• Pemetrexed in the treatment of malignant mesothelioma: results from an expanded access program in Germany — M. Reck, R.A. Stahel, et al. (2010)

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