Pemetrexed in malignant pleural mesothelioma and the clinical outcome

Our plain-English summary of Pemetrexed in malignant pleural mesothelioma and the clinical outcome, by A. Knuuttila, E.R. Salomaa, S. Saikkonen, et al (The Clinical Respiratory Journal, 2012).

The study

• Authors: A. Knuuttila, E.R. Salomaa, S. Saikkonen, S. Hurme, J. Salo
• Journal: The Clinical Respiratory Journal
• Published: 2012;6(2):96-103
• Cited by: 4 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Introduction: Pemetrexed has emerged as standard chemotherapy for malignant pleural mesothelioma (MPM).

Objectives: MPMs at two Finnish University Hospitals during 7 years (2000-2006) were reviewed in order to evaluate the treatments, survival and prognostic factors. The results in two periods (before pemetrexed use in 2000-2002 and with pemetrexed in 2003-2006) were compared.

Methods: Data were collected from the individual patient records retrospectively, and analysed.

Results: Altogether 197 patients were diagnosed with following histologies: 136 (69%) epithelioid, 19 (10%) sarcomatoid, 17 (9%) mixed, 25 (13%) not specified; 141 (72%) patients received treatment (five extrapleural pneumonectomy, 36 pleurectomy/decortication, 126 chemotherapy). Median survival was 12.9 months and the 1-, 2- and 3-year survivals were 51.8%, 21.8% and 12.1%, respectively. Univariate analysis showed no significant difference in survival between the patients diagnosed before or during the pemetrexed era (P = 0.124). The patients receiving pemetrexed or other chemotherapy had median survivals of 16.7 and 15.3 months, respectively. The independent prognostic factors for survival were histology and asbestos exposure. Non-epithelioid histology yielded 17 times higher risk of dying than epithelioid. Asbestos exposure doubled the risk of dying, but only in patients diagnosed in 2003-2006.

Conclusions: Pemetrexed is beneficial for selected patients, but it has not changed the outcome of the whole MPM population as much as perhaps anticipated. Patient groups with various treatments or symptomatic care only reached survival results comparable to those reported in chemotherapy trials, thus emphasising the need for better subtyping of mesothelioma and individualising the treatment.

© 2011 Blackwell Publishing Ltd.

In plain English

This retrospective review of patient records covered all 197 people diagnosed with malignant pleural mesothelioma at two Finnish university hospitals, Helsinki and Turku, from 2000 to 2006. The authors compared patients diagnosed before pemetrexed, a chemotherapy drug, came into use (2000–2002, 75 patients) with those diagnosed after (2003–2006, 122). Occupational asbestos exposure was recorded for 146 patients (74%). Fiber types were not reported. Median survival overall was 12.9 months, with no significant survival difference between the periods. Patients given pemetrexed had a median survival of 16.7 months, against 10.2 months for others, but the authors noted that treatment choice depends on factors affecting prognosis. Among patients diagnosed from 2003 on, asbestos exposure was associated with double the risk of dying compared with no exposure (hazard ratio 2.014, 95% confidence interval 1.074 to 3.775), but not among those diagnosed earlier. Sarcomatoid, mixed or unspecified tumours carried a higher risk of dying than epithelioid tumours (hazard ratio 1.739, 95% confidence interval 1.261 to 2.398). The authors concluded that pemetrexed most likely helped individual patients but showed no marked benefit for the whole population.

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 review of hospital patient records (cohort), comparing patients diagnosed before (2000–2002) and during (2003–2006) the period of pemetrexed use
• Who was studied: 197 patients with malignant pleural mesothelioma (peritoneal and pericardial excluded) at Helsinki (131) and Turku (66) University Hospitals, Finland, January 2000 to December 2006; 75 diagnosed 2000–2002 and 122 diagnosed 2003–2006; 81% male, median age 65.6 years
• Exposure: The main comparison was treatment: pemetrexed (alone or with cisplatin or carboplatin) versus other chemotherapy, surgery, radiotherapy or symptomatic care only. Occupational asbestos exposure, taken from patient records, was analysed as a prognostic factor and was reported in 146 (74%) patients, 6 of them women. No fiber types or doses were given.
• Main results:
  • In the whole population (197 patients), median survival was 12.9 months.
  • In the whole population, survival was 51.8% at 1 year, 21.8% at 2 years and 12.1% at 3 years after diagnosis.
  • Survival did not differ significantly between patients diagnosed before the pemetrexed era (2000–2002) and during it (2003–2006) (log-rank P = 0.124).
  • In the whole population, patients who received pemetrexed had a median survival of 16.7 months, against 10.2 months for patients who did not (log-rank P less than 0.0001).
  • In the earlier era, patients who received chemotherapy other than pemetrexed had a median survival of 15.3 months, against 10.5 months for patients who received other modes of therapy. This difference was not statistically significant.
  • Patients given symptomatic therapy only (56 patients) had a median survival of 5.5 months, but 8 of the 56 survived over 24 months.
  • Median survival was 14.6 months for epithelioid histology and 8.9 months for other histology. In multivariate analysis, the pooled group of sarcomatoid, mixed or not-otherwise-specified histology (61 patients) had a hazard ratio of 1.739 (95% CI 1.261 to 2.398) compared with epithelioid (136 patients).
  • Among patients diagnosed in 2003 or later, those with asbestos exposure (96) had a hazard ratio of 2.014 (95% CI 1.074 to 3.775) for dying compared with those without exposure (26). Among patients diagnosed before 2003, the hazard ratio for exposed (50) versus unexposed (25) patients was 0.841 (95% CI 0.460 to 1.540).
  • Among patients without asbestos exposure, diagnosis in 2003 or later carried a 64% smaller risk of dying than diagnosis before 2003 (hazard ratio 0.361, 95% CI 0.185 to 0.706). Among exposed patients, the risk did not change over time (hazard ratio 0.865, 95% CI 0.605 to 1.238).
  • Laterality of disease, gender and smoking history were not independent prognostic factors.
• The authors' conclusion: The authors concluded that pemetrexed most likely improved survival for individual patients, but that its introduction did not show a marked benefit for the whole mesothelioma population. They also concluded that mesothelioma cannot be treated as one type of malignancy with a single treatment approach.
• Limitations the authors state:
  • The authors acknowledged it can be argued whether patients at two university hospitals represent mesothelioma patients generally.
  • Because the study was retrospective, the way patients were selected into different treatments creates a bias.
  • The choice of treatment depends on factors that influence prognosis. Patients in poorer condition or with more extensive disease tend to receive symptomatic therapy only.
  • Disease stage was not reviewed.
  • Tumour responses and time to progression were not determined, because the records were not expected to be detailed enough.
  • The benefit of surgery could not be truly evaluated, because most patients had widely spread tumours at presentation.

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), Pleural Mesothelioma, Chemotherapy, Epithelioid, Sarcomatoid, Extrapleural Pneumonectomy (EPP), Pleurectomy/Decortication (P/D), Median Survival.

Related studies

• New tricks for old biomarkers: thymidylate synthase expression as a predictor of pemetrexed activity in malignant mesothelioma — P.A. Zucali, E. Giovannetti, et al. (2010)
• Retreatment with pemetrexed-based chemotherapy in patients with malignant pleural mesothelioma — G.L. Ceresoli, P.A. Zucali, et al. (2011)
• 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)
• Pemetrexed for malignant pleural mesothelioma: Is it a standard second-line therapy? — K. Tamura, Y. Fujiwara (2010)
• Can pemetrexed help in malignant mesothelioma? — (2006)

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