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

详细信息	查看全文 | 推荐本文 |

• 作者：Prof Chandra P Belani ; MD^a ; ^{cbelani@psu.edu} ; Thomas Brodowicz ; MD^b ; Tudor E Ciuleanu ; MD^c ; Prof Maciej Krzakowski ; MD^d ; Sung Hyun Yang ; MD^e ; Fá ; bio Franke ; MD^f ; Branka Cucevic ; MD^g ; Jayaprakash Madhavan ; MD^h ; ⁱ ; Armando Santoro ; MD^j ; Rodryg Ramlau ; MD^k ; ^l ; Astra M Liepa ; PharmD^m ; Carla Visseren-Grul ; MDⁿ ; Patrick Peterson ; PhD^m ; William J John ; MD^m ; Prof Christoph C Zielinski ; MD^b
• 刊名：Lancet Oncology
• 出版年：2012
• 期刊代码：184_14702045
• 类别：med
• 出版时间：March, 2012
• 卷：13
• 期：3
• 页码：292-299
• 文件大小：229 K

摘要

| Figures/TablesFigures/Tables | ReferencesReferences

Summary

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/m² 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 , number .

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路76, 95%CI 0路59-0路99; p=0路041) and haemoptysis (HR 0路58, 95%CI 0路34-0路97; p=0路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路3 mm vs 0路2 mm; p=0路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路001), transfusions (42 [10%] vs seven [3%]; p=0路003), and erythropoiesis-stimulating agents (26 [6%] vs four [2%]; p=0路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.