Second-line treatment for malignant pleural mesothelioma

Our plain-English summary of Second-line treatment for malignant pleural mesothelioma, by G.L. Ceresoli, P.A. Zucali, L. Gianoncelli, et al (Cancer Treatment Reviews, 2010).

The study

• Authors: G.L. Ceresoli, P.A. Zucali, L. Gianoncelli, E. Lorenzi, A. Santoro
• Journal: Cancer Treatment Reviews
• Published: 2010;36(1):24-32
• Type of article: Review
• Cited by: 51 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Most patients affected by malignant pleural mesothelioma (MPM) are candidates for chemotherapy during the course of the disease, as single modality treatment or within the context of a multimodality approach. Following the results of a large phase III trial, the combination of cisplatin and pemetrexed has become the preferred first-line chemotherapy, although there is also evidence for the activity of the combination with carboplatin based on phase II studies. Unfortunately, nearly all MPM patients progress during or after first-line treatment. Second-line therapies are being increasingly used in the clinical practice because patients are frequently still healthy at the time of disease progression. However, the role of these treatments in MPM is unproven, and the optimal regimens still remain to be defined. In pemetrexed-naïve patients, data from a randomized trial vs. best supportive care suggest the use of single-agent pemetrexed as a standard second-line treatment. This evidence is supported also by the results of the Expanded Access Programs. To date, there is still no standard approach for the growing population of pemetrexed-pre-treated patients. In selected cases with a prolonged response to first-line pemetrexed-based chemotherapy, re-treatment with a pemetrexed-based regimen should be considered. When a trial is not available or patients are not eligible for an experimental approach, single-agent vinorelbine can be a reasonable option for palliation. However, second-line therapy in MPM remains an ideal field in which to test new chemotherapy agents as well as new therapeutic strategies, including anti-angiogenic compounds, small molecules or monoclonal antibodies that target different molecular pathways.

2009 Elsevier Ltd. All rights reserved.

In plain English

This article was a review, not a new study. The authors searched PubMed, Cancerlit and conference abstracts on second-line treatment of malignant pleural mesothelioma, given when cancer progressed during or after first-line chemotherapy; a trials registry supplied ongoing-trial data. Some reviewed studies were reported by members of this author group. For patients never given pemetrexed, they described a randomized phase III trial of 243 patients. Disease control was 59.3% with pemetrexed versus 19.2% with best supportive care alone; median time to progression was 3.8 versus 1.5 months. Median overall survival did not differ significantly (8.4 versus 9.7 months), possibly because supportive-care patients more often received later chemotherapy. For pemetrexed-treated patients, the authors noted that prospective chemotherapy trials were lacking and no drug or combination was approved. The authors concluded that second-line therapy's role had yet to be proved and that single-agent pemetrexed was supported as standard second-line treatment for pemetrexed-naïve patients. They also concluded that pemetrexed-containing re-treatment should be considered in selected patients with a prolonged response to first-line pemetrexed-based chemotherapy, based on preliminary evidence from small case series.

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: Review of published literature and conference abstracts on second-line therapy for malignant pleural mesothelioma, with an overview of ongoing trials
• Who was studied: No new patients were studied. The review covered patients with malignant pleural mesothelioma in published trials, case series and congress abstracts found through PubMed and Cancerlit searches. Information on ongoing trials came from the clinicaltrials.gov registry. Some reviewed studies were reported by members of this author group, for example Zucali and Ceresoli.
• Exposure: Not an asbestos exposure study. The treatments reviewed were second-line drug therapies: chemotherapy (pemetrexed alone or with cisplatin or carboplatin, vinorelbine, gemcitabine, oxaliplatin and others) and targeted agents.
• Main results:
  • The review included studies reported by members of the author group, such as the Zucali et al. study of gemcitabine plus vinorelbine.
  • A randomized phase III trial compared pemetrexed plus best supportive care with best supportive care alone and enrolled 243 patients. Disease control was 59.3% in the pemetrexed arm and 19.2% in the supportive-care arm (P < .0001).
  • In the same trial, median time to progression was significantly longer in the pemetrexed arm (3.8 vs. 1.5 months).
  • In the same trial, median overall survival did not differ significantly: 8.4 months with pemetrexed vs. 9.7 months with supportive care only.
  • Patients in the supportive-care arm received post-study chemotherapy significantly more often and earlier, which the authors suggested may explain the survival result.
  • For patients previously treated with pemetrexed, the authors noted that prospective chemotherapy trials were lacking.
  • For patients previously treated with pemetrexed, the authors stated there was no approved drug or drug combination for second-line therapy.
  • The authors' recommendation on pemetrexed re-treatment applied to selected cases with a prolonged response to first-line pemetrexed-based chemotherapy.
• The authors' conclusion: The authors concluded that, in pemetrexed-naïve patients, the randomized trial and the Expanded Access Programs support single-agent pemetrexed as a standard second-line treatment. They concluded that second-line therapy's overall role had yet to be proved.
• Limitations the authors state:
  • The authors stated that the role of second-line therapy in this disease had yet to be proved.
  • The authors noted that their conclusion favoring re-treatment with a pemetrexed-containing regimen rested only on preliminary evidence from small case series. That conclusion applied to selected cases with a prolonged response to first-line pemetrexed-based chemotherapy.

Topics

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

Medical terms in this study, explained in our Lexicon: Pleural Mesothelioma, Chemotherapy, Cisplatin, Pemetrexed (Alimta), Carboplatin, Disease Progression, Vinorelbine, Second-Line Therapy.

Related studies

• Gemcitabine and vinorelbine as second-line or beyond treatment in patients with malignant pleural mesothelioma pretreated with platinum plus pemetrexed chemotherapy — G. Toyokawa, M. Takenoyama, et al. (2014)
• Pemetrexed for malignant pleural mesothelioma: Is it a standard second-line therapy? — K. Tamura, Y. Fujiwara (2010)
• Retreatment with pemetrexed-based chemotherapy in patients with malignant pleural mesothelioma — G.L. Ceresoli, P.A. Zucali, et al. (2011)
• Second-line chemotherapy in malignant pleural mesothelioma: results of a retrospective multicenter survey — P.A. Zucali, M. Simonelli, 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)
• COX-2 specific inhibitors enhance the cytotoxic effects of pemetrexed in mesothelioma cell lines — S.L. O'Kane, G.L. Eagle, et al. (2010)

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