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.

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.

Docetaxel in combination with platinums (cisplatin or carboplatin) in advanced and metastatic non-small cell lung cancer.

In a large, multinational, randomized phase III trial, 1,220 patients with advanced and/or metastatic non-small cell lung cancer were randomized to receive one of three treatments: docetaxel 75 mg/m(2) plus cisplatin 75 mg/m(2) every 3 weeks; docetaxel 75 mg/m(2) plus carboplatin to an AUC of 6 every 3 weeks; or a standard reference arm of vinorelbine given at 25 mg/m(2) on days 1, 8, 15, and 22 plus cisplatin 100 mg/m(2) on day 1 every 4 weeks. The choice of treatment and dose was based on a series of four phase II studies that indicated the combination of docetaxel (75 to 100 mg/m(2)) and cisplatin (75 to 100 mg/m(2)) was active and feasible; carboplatin may have a more favorable therapeutic index than cisplatin, particularly with regard to nonhematologic toxicities, and had proven activity in combination with docetaxel in phase II study; and randomized studies had shown the combination of vinorelbine plus cisplatin was superior to either vinorelbine alone or cisplatin alone and was considered as a reference study regimen in the clinical setting upon initiation of this phase III study. Preliminary results of the phase III trial showed that the overall survival among patients randomized to receive docetaxel plus cisplatin was significantly better than that among patients treated with vinorelbine/cisplatin and similar between the docetaxel plus carboplatin versus control arm. The three arms were similar for toxicity data, except the use of vinorelbine plus cisplatin was associated with a significantly greater incidence of grade (3/4) anemia and nausea and vomiting than use of docetaxel plus either cisplatin or carboplatin.