Lung Cancer Survival Improved By Maintenance Therapy With Pemetrexed

Main Category: Lung Cancer
Article Date: 22 Sep 2009 - 0:00 PDT

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Giving pemetrexed maintenance therapy to patients with non-small-cell lung cancer (NSCLC) who have not had disease progression after initial platinum-based chemotherapy improves both overall and progression-free survival. The findings are discussed in an Article published Online First and in an upcoming edition of The Lancet, written by Dr Chandra Belani, Penn State Hershey Cancer Institute, Hershey, PA, USA, and colleagues.

More than 1 million people worldwide die every year from lung cancer, and more than 87% of these cases are non-small-cell lung cancer. About 40% of patients have advanced disease at presentation. Historically, standard first-line platinum-based chemotherapy has provided modest improvements in overall survival. However, less than 40% of patients show significant tumour reduction. Therefore, opportunities clearly exist to improve the clinical benefit of first-line treatment for patients before disease progression. In this study, the authors assessed pemetrexed as maintenance therapy as part of first-line treatment-in patients who had received four cycles of platinum-based chemotherapy and not had disease progression.

This randomised phase III study took place in 83 centres in 20 countries. 663 patients with advanced NSCLC who had not progressed on four cycles of platinum-based chemotherapy were randomly assigned (2:1 ratio) to receive pemetrexed (500 mg/m², day 1) plus best supportive care (441 patients) or placebo plus best supportive care (222) in 21-day cycles until disease progression. The primary endpoint was progression-free survival and the secondary endpoint overall survival.

The researchers found that pemetrexed significantly improved progression-free survival (4•3 months vs 2•6 months); and overall survival (13•4 months vs 10•6 months) compared with placebo. Put another way, pemetrexed treatment resulted in a 50% reduction in the risk of disease progression or death; and a 21% reduction in the risk of death only. Treatment discontinuations due to drug-related toxic effects were higher in the pemetrexed group than in the placebo group (21 [5%] vs three [1%]). Drug-related grade three or higher toxic effects were higher with pemetrexed than with placebo (70 [16%] vs nine [4%]; p<0•0001), specifically fatigue (22 [5%] vs one [1%]) and neutropenia (13 [3%] vs 0). No pemetrexed-related deaths occurred. A smaller proportion patients in the pemetrexed group than in the placebo group received systemic post-discontinuation therapy (227 [51%] vs 149 [67%]. Post-discontinuation therapy is treatment at second-line or progression and beyond.

The authors conclude: "Pemetrexed maintenance therapy is well tolerated and offers significantly improved progression-free and overall survival compared with placebo, making it a new treatment option for patients with advanced non-squamous non-small-cell lung cancer who do not progress after initial induction therapy."

In an accompanying Comment, Dr Thomas Stinchcombe, Lineberger Comprehensive Cancer Center at the University of Chapel Hill, North Carolina, USA, and Dr Howard West, Swedish Cancer Institute, Seattle, WA, USA, say that the strategy of using pemetrexed as maintenance therapy 'merits being considered as a strong option, reflected by the recent approval of pemetrexed in this setting by both the European Medicines Agency and The US Food and Drug Administration.'

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The Lancet