Pemetrexed as second-line therapy for advanced non-small-cell lung cancer (NSCLC)

Our plain-English summary of Pemetrexed as second-line therapy for advanced non-small-cell lung cancer (NSCLC), by E. Felip, R. Rosell (Therapeutics and Clinical Risk Management, 2008).

The study

• Authors: E. Felip, R. Rosell
• Journal: Therapeutics and Clinical Risk Management
• Published: 2008;4(3):579-85
• Cited by: 9 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

NSCLC accounts for 80% of all cases of lung cancer, which is the leading cause of cancer mortality. The majority of NSCLC patients present with advanced, unresectable disease, which remains incurable. In advanced disease, chemotherapy with platinum (cisplatin or carboplatin) in combination with a third-generation cytotoxic drug (vinorelbine, gemcitabine, paclitaxel, or docetaxel) can provide a modest improvement in survival without impairing quality of life. In chemotherapy-naïve, advanced, non-squamous NSCLC patients, the combination of bevacizumab with chemotherapy was shown to produce better outcomes than chemotherapy alone. Response rates of 20%-40% can now be expected, with a median survival of 8-11 months and a 1-year survival rate of 30%-40%. In second-line treatment, docetaxel has shown superiority to best supportive care in terms of survival and quality of life. A pooled analysis comparing docetaxel administered weekly versus 3-weekly found similar survival rates between the schedules and a non-significant reduction in febrile neutropenia for the weekly regimen. Pemetrexed, a multitargeted antifolate agent, has shown clear activity in several tumors, including mesothelioma and NSCLC. In a phase III trial, second-line treatment with pemetrexed demonstrated overall survival comparable to docetaxel, with a more manageable toxicity profile.

In plain English

This article was a review, not a new study. The authors summarized published trials and conference reports on the cancer drug pemetrexed in advanced non-small-cell lung cancer (NSCLC). The article was not about asbestos, and its main text did not discuss mesothelioma. The review centered on a phase III trial by Hanna and colleagues (2004), in which 571 eligible patients whose cancer had come back after earlier chemotherapy were randomized to pemetrexed or docetaxel. As the review reported, median survival in that trial was 8.3 months with pemetrexed and 7.9 months with docetaxel, and the 1-year survival rate was 29.7% in each arm. The docetaxel arm had more severe (grade 3/4) neutropenia (40% vs 5%), more neutropenic fever (13% vs 2%) and more neuropathy (8% vs 3%) than the pemetrexed arm. The review also described a trial of 588 eligible patients. It found no survival difference between a higher pemetrexed dose (900 mg/m2) and the standard dose (500 mg/m2). The authors concluded that pemetrexed, given with folic acid and vitamin B12, showed comparable efficacy and a better toxicity profile than docetaxel as second-line treatment.

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: Narrative review of clinical trials and conference reports on pemetrexed in non-small-cell lung cancer
• Who was studied: Patients with advanced non-small-cell lung cancer in the trials reviewed. The main second-line trial reviewed (Hanna et al 2004) randomized 571 eligible previously treated (relapsed) patients.
• Exposure: No asbestos or fiber exposure was studied. The subject was treatment with the chemotherapy drug pemetrexed, compared mainly with docetaxel in second-line treatment and given with folate and B12 supplementation.
• Main results:
  • In the reviewed phase III trial (Hanna et al 2004), median survival was 8.3 months in the pemetrexed arm and 7.9 months in the docetaxel arm, and response rates were 9.1% and 8.8% respectively.
  • In the same trial, median progression-free survival was 2.9 months and the 1-year survival rate was 29.7% in each arm.
  • The docetaxel arm had more grade 3/4 neutropenia (40% vs 5%), neutropenic fever (13% vs 2%) and neuropathy (8% vs 3%) than the pemetrexed arm.
  • In a reviewed trial by Cullen et al (2007) of 588 eligible patients, median survival was 6.7 months with the standard dose (500 mg/m2) and 6.9 months with the higher dose (900 mg/m2). No differences were detected in survival, progression-free survival or response rate.
  • In a reviewed first-line phase III trial (Scagliotti et al 2007b) of 1725 randomized patients, overall survival with pemetrexed/cisplatin was non-inferior to gemcitabine/cisplatin (10.3 vs 10.3 months; HR = 0.94).
• The authors' conclusion: The authors concluded that as second-line treatment for advanced NSCLC, pemetrexed given with folic acid and vitamin B12 showed comparable efficacy and a better toxicity profile than docetaxel. They also stated that targeted-agent combinations and pharmacogenomic approaches were still being evaluated.

Topics

Medical terms in this study, explained in our Lexicon: Pemetrexed (Alimta), Second-Line Therapy, Lung Cancer, Unresectable, Chemotherapy, Cisplatin, Carboplatin, Vinorelbine.

Related studies

• Pemetrexed as first-line therapy for non-squamous non-small cell lung cancer — S. Ricciardi, S. Tomao, et al. (2009)
• Mathematical modeling for Phase I cancer trials: A study of metronomic vinorelbine for advanced non-small cell lung cancer (NSCLC) and mesothelioma patients — F. Barlesi, D.C. Imbs, et al. (2017)
• Pemetrexed for malignant pleural mesothelioma: Is it a standard second-line therapy? — K. Tamura, Y. Fujiwara (2010)
• Pemetrexed Maintenance Therapy Following Bevacizumab-Containing First-Line Chemotherapy in Advanced Malignant Pleural Mesothelioma: A Case Report and Literatures Review — X.Q. Jing, L. Zhou, et al. (2016)
• Sunitinib combined with pemetrexed and cisplatin: results of a phase I dose-escalation and pharmacokinetic study in patients with advanced solid malignancies, with an expanded cohort in non-small cell lung cancer and mesothelioma — D.R. Camidge, N. Blais, et al. (2013)
• A phase II clinical trial of the vascular disrupting agent BNC105P as second line chemotherapy for advanced Malignant Pleural Mesothelioma — A.K. Nowak, C. Brown, et al. (2013)

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