Quality of life assessment of second-line docetaxel versus best supportive care in patients with non-small-cell lung cancer previously treated with platinum-based chemotherapy: results of a prospective, randomized phase III trial

Abstract

Purpose and methods: Docetaxel second-line chemotherapy for non-small-cell lung cancer (NSCLC) has previously been shown to improve survival significantly compared with best supportive care (BSC). This multicenter phase III trial prospectively investigated quality of life (QOL) in NSCLC patients treated with either second-line docetaxel or BSC. Patients with stage IIIB/IV NSCLC, performance status ≤2, and adequate biochemistry and hematology were eligible if they had received ≥1 platinum-based chemotherapy regimens. Patients were randomized to docetaxel 100 mg/m² (n=49) or, after protocol amendment, to docetaxel 75 mg/m² (n=55), or to BSC (n=100), with Lung Cancer Symptom Scale (LCSS) and/or QLQ-C30 (with LC13 module) assessment every 3 weeks. Results: Longitudinal analysis including all available assessments over time showed statistically significant differences in patient-rated pain scores in favor of docetaxel overall (P=0.005) or docetaxel 100 mg/m² (P=0.003) compared to BSC. Trends in favor of docetaxel were noted on observer-rated scales for fatigue and pain for all docetaxel patients, and for total LCSS score, appetite and fatigue with docetaxel 100 mg/m². Changes from baseline to the last available assessment (end point) showed significantly (P<0.05) less deterioration in LCSS pain score in patients with docetaxel (75 and 100 mg/m² combined) than with BSC. An improved mean pain score with docetaxel 100 mg/m² was contrasted with a deterioration in mean pain score with BSC (P<0.01). There was also significantly less deterioration in the global QOL today score with docetaxel 100 mg/m² (P<0.01). Similar trends were recorded with QLQ-C30 assessments. Conclusions: Second-line docetaxel therapy for advanced NSCLC significantly improves survival with a trend towards less deterioration in QOL compared with BSC.

Introduction

Non-small-cell lung cancer (NSCLC) accounts for approximately 75–85% of all lung cancer cases [1], [2], [3]. Fewer than 25% of patients have resectable disease on presentation, and the rest have locally advanced or incurable metastatic disease [4]. Overall 5-year survival is approximately 13%, and ranges from 46% in patients with localized disease to <1% in those with advanced metastatic NSCLC [1]. The goal of treatment for patients with recurrent or metastatic NSCLC is palliative.

Experience over the past two decades has shown improvements in survival, symptom control and quality of life (QOL) in patients with metastatic NSCLC who receive first-line chemotherapy [5], [6], [7]. Despite the advances in management over the past decade, substantial numbers of patients with NSCLC fail to respond to, or progress, after conventional first-line platinum-based chemotherapy.

Uncontrolled phase II trials of third generation chemotherapy agents suggested that pretreated patients might derive benefit from second-line chemotherapy [8], [9], [10], [11], [12]. Docetaxel in particular showed consistent activity in this refractory population, with several phase II trials in over 300 patients reporting overall response rates of 14–27% and median survival exceeding 7 months after treatment with 100 mg/m² every 3 weeks (20 patients received docetaxel 75 mg/m² and 22 received docetaxel 60 mg/m²) [8], [13], [14], [15], [16], [17], [18], [19]. Because of these encouraging phase II results, docetaxel was evaluated in randomized trials to confirm its efficacy in this patient population.

In the TAX 317 trial, a prospective, open-label, multicenter phase III comparison of second-line docetaxel with best supportive care (BSC), 204 previously treated patients with stage IIIB/IV NSCLC entered the study, and 104 received second-line therapy (49 received 100 mg/m² and 55 received 75 mg/m² dose). Consistent with phase II findings, the study showed significant improvements in time to progression (10.6 weeks versus 6.7 weeks; P<0.001) and median survival (7.0 months versus 4.6 months; log-rank test, P=0.047) in docetaxel recipients [20].

Because benefits of treatment must outweigh risks, patient-focused outcomes and optimization of well-being are of paramount importance in individuals who have limited life expectancy [21], [22]. Thus, a QOL analysis was also performed in this phase III study. These data, which are presented in this article, were obtained using the Lung Cancer Symptom Scale (LCSS) and European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 (with LC13 lung cancer module) instruments [23], [24]. Both of these are validated QOL scales for patients with lung cancer.