Quality of life in patients with advanced non-small-cell lung cancer given maintenance treatment with pemetrexed versus placebo (H3E-MC-JMEN): Results from a randomised, double-blind, phase 3 study

Chandra Belani, Thomas Brodowicz, Tudor E. Ciuleanu, Maciej Krzakowski, Sung Hyun Yang, Fábio Franke, Branka Cucevic, Jayaprakash Madhavan, Armando Santoro, Rodryg Ramlau, Astra M. Liepa, Carla Visseren-Grul, Patrick Peterson, William J. John, Christoph C. Zielinski

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Abstract

Background: Pemetrexed maintenance therapy significantly improved overall survival and progression-free survival compared with placebo, and had a good safety profile in a phase 3 placebo-controlled study in patients with advanced non-small-cell lung cancer (NSCLC). Results for quality of life, symptom palliation, and tolerability are presented here. Methods: After four cycles of platinum-based induction therapy, 663 patients with stage IIIB or stage IV NSCLC and Eastern Cooperative Oncology Group performance status of 0 or 1 were randomly assigned (in a 2:1 ratio) from March 15, 2005, to July 20, 2007, using the Pocock and Simon minimisation method to receive pemetrexed (500 mg/m 2 every 21 days; n=441) or placebo (n=222) plus best supportive care until disease progression. The primary efficacy data have been reported previously. Patients completed the Lung Cancer Symptom Scale (LCSS) at baseline, after each cycle, and post-discontinuation. Worsening of symptoms was defined as an increase of 15 mm or more from baseline on a 100 mm scale for each LCSS item. The primary outcome for these quality-of-life analyses was time to worsening of symptoms, analysed for all randomised patients. This study is registered with ClinicalTrials.gov, number NCT00102804. Findings: Baseline characteristics, including LCSS scores, were well balanced between groups. Baseline LCSS scores were low, indicating low symptom burden for patients without disease progression after completion of first-line treatment. Longer time to worsening was recorded for pain (hazard ratio [HR] 0·76, 95% CI 0·59-0·99; p=0·041) and haemoptysis (HR 0·58, 95% CI 0·34-0·97; p=0·038) with pemetrexed than with placebo; no other significant differences in analyses of time to worsening were noted. Additional longitudinal analyses showed a greater increase in loss of appetite in the pemetrexed group than in the placebo group (4·3 mm vs 0·2 mm; p=0·028). Rates of resource use were statistically higher for pemetrexed than for placebo: admissions to hospital for drug-related adverse events (19 [4%] vs none; p=0·001), transfusions (42 [10%] vs seven [3%]; p=0·003), and erythropoiesis-stimulating agents (26 [6%] vs four [2%]; p=0·017). Interpretation: Quality of life during maintenance therapy with pemetrexed is similar to placebo, except for a small increase in loss of appetite, and significantly delayed worsening of pain and haemoptysis. In view of the improvements in overall and progression-free survival noted with pemetrexed maintenance therapy, such treatment is an option for patients with advanced non-squamous NSCLC who have not progressed after platinum-based induction therapy. Funding: Eli Lilly.

Original languageEnglish (US)
Pages (from-to)292-299
Number of pages8
JournalThe Lancet Oncology
Volume13
Issue number3
DOIs
StatePublished - Mar 1 2012

All Science Journal Classification (ASJC) codes

  • Oncology

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    Belani, C., Brodowicz, T., Ciuleanu, T. E., Krzakowski, M., Yang, S. H., Franke, F., Cucevic, B., Madhavan, J., Santoro, A., Ramlau, R., Liepa, A. M., Visseren-Grul, C., Peterson, P., John, W. J., & Zielinski, C. C. (2012). Quality of life in patients with advanced non-small-cell lung cancer given maintenance treatment with pemetrexed versus placebo (H3E-MC-JMEN): Results from a randomised, double-blind, phase 3 study. The Lancet Oncology, 13(3), 292-299. https://doi.org/10.1016/S1470-2045(11)70339-4