Re-challenge with pemetrexed in advanced mesothelioma: a multi-institutional experience

Our plain-English summary of Re-challenge with pemetrexed in advanced mesothelioma: a multi-institutional experience, by A. Bearz, R. Talamini, G. Rossoni, et al (BMC Research Notes, 2012).

The study

• Authors: A. Bearz, R. Talamini, G. Rossoni, A. Santo, V. de Pangher, G. Fasola, F. Rosetti, A. Favaretto, V. Gregorc, M. Berretta, S. Santarossa, E. Berto, U. Tirelli
• Journal: BMC Research Notes
• Published: 2012;5:482
• Cited by: 31 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Background: Although first-line therapy for patients affected by advanced mesothelioma is well established, there is a lack of data regarding the impact of second-line treatment.

Methods: We retrospectively collected data of patients affected by advanced mesothelioma, already treated with first-line therapy based on pemetrexed and platin, with a response (partial response or stable disease) lasting at least 6 months, and re-treated with a pemetrexed-based therapy at progression. The primary objective was to describe time to progression and overall survival after re-treatment.

Results: Overall across several Italian oncological Institutions we found 30 patients affected by advanced mesothelioma, in progression after a 6-month lasting clinical benefit following a first-line treatment with cisplatin and pemetrexed, and re-challenged with a pemetrexed-based therapy. In these patients we found a disease control rate of 66%, with reduction of pain in 43% of patients. Overall time to progression and survival were promising for a second-line setting of patients with advanced mesothelioma, being 5.1 and 13.6 months, respectively.

Conclusions: In our opinion, when a patient has a long-lasting benefit from previous treatment with pemetrexed combined with a platin compound, the same treatment should be offered at progression.

In plain English

This retrospective study collected 30 patients with advanced malignant mesothelioma from seven Italian institutions between January 2005 and December 2009. All had received first-line chemotherapy combining pemetrexed with cisplatin or carboplatin. Their tumors had partly shrunk or stayed stable, with at least 6 months from the end of first-line chemotherapy to radiological progression. They were then treated again with pemetrexed, either alone (9 patients) or with carboplatin (16) or cisplatin (5). Sixteen (53%) had a history of asbestos exposure; for the others it was unknown or unclear. After re-treatment, 5 patients had a partial response, 15 had stable disease and 10 progressed. The authors counted this as disease control in 20 of 30 (66%). Time to progression was 5.1 months and median overall survival 13.6 months. Pain decreased in 13 of 30 patients (43%) and worsened in 10 (33%). Time to progression did not differ significantly between combination therapy and pemetrexed alone (5.7 versus 4 months). The authors noted that their patients were selected for good prognostic factors. In their opinion, when there are no other effective strategies, patients with a long-lasting benefit from platin-pemetrexed should be offered the same drugs again at progression.

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 multi-institutional analysis (case series) of patients re-treated with pemetrexed-based chemotherapy as second-line therapy
• Who was studied: 30 patients with advanced malignant mesothelioma from 7 Italian institutions (Aviano, Milan, Verona, Gorizia, Udine, Mirano, Padova), collected between January 2005 and December 2009. 77% were male and median age at diagnosis was 64.1 years. One patient had disease in the tunica vaginalis. All had partial response or stable disease after first-line pemetrexed-platin. For all of them, the time from the end of first-line chemotherapy to radiological progression was at least 6 months.
• Exposure: The study examined treatment rather than an exposure: second-line re-treatment with pemetrexed (500 mg/m2 every three weeks), alone (9 patients) or combined with carboplatin (16) or cisplatin (5). Asbestos exposure history was reported for 16 patients (53%) and was unknown or unclear for the rest.
• Main results:
  • Response after re-treatment in the 30 patients: 15 (50%) stable disease, 5 (17%) partial response, 10 (33%) disease progression
  • The authors reported clinical benefit (disease control: partial response plus stable disease) in 20 of 30 patients (66%)
  • Time to progression from the start of re-treatment was 5.1 months for all 30 patients
  • Time to progression did not differ significantly between patients re-treated with pemetrexed plus platin (5.7 months) and pemetrexed alone (4 months)
  • Median overall survival from the start of re-treatment was 13.6 months; by the end of June 2011, 20 patients had died and 10 were still alive
  • Pain decreased in 13 of 30 patients (43%). 7 (23%) had no pain at all, and 10 (33%) reported worse pain.
  • Modified RECIST radiological assessment was available for 26 of 30 patients. In 3, progression was a relapse of pleural effusion, and for 1 the images could not be retrieved.
• The authors' conclusion: In the authors' opinion, when a patient has had a long-lasting benefit from pemetrexed combined with a platin compound, the same treatment should be offered at progression. They added that this applies in the absence of other effective strategies, because symptoms can still improve and time to progression can still be gained.
• Limitations the authors state:
  • The patients were selected for good prognostic factors: performance status, benefit from first-line treatment, and a fairly long time to progression after first-line treatment.
  • No patient had pure sarcomatoid histology, which the authors describe as one of the worst prognostic factors.
  • The slightly better time to progression with combination re-treatment was not statistically significant. It may only reflect better performance status or younger age guiding the choice of treatment.

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), Mesothelioma, First-line Therapy, Overall Survival, Cisplatin, Second-Line Therapy.

Related studies

• Pemetrexed re-challenge in pleural malignant mesothelioma: an option for a subset of patients initially treated with pemetrexed-platinum doublets in the first-line setting? — G. Zalcman, E. Bergot, et al. (2011)
• Fatal pemetrexed-induced lung injury in patients with advanced mesothelioma: a report of two cases — K. Nagata, R. Kaji, et al. (2010)
• Pemetrexed in malignant pleural mesothelioma and the clinical outcome — A. Knuuttila, E.R. Salomaa, et al. (2012)
• 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)

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