Palliative chemotherapy beyond three courses conveys no survival or consistent quality-of-life benefits in advanced non-small-cell lung cancer

Abstract

This randomised multicentre trial was conducted to establish the optimal duration of palliative chemotherapy in advanced non-small-cell lung cancer (NSCLC). We compared a policy of three vs six courses of new-generation platinum-based combination chemotherapy with regard to effects on quality of life (QoL) and survival. Patients with stage IIIB or IV NSCLC and WHO performance status (PS) 0-2 were randomised to receive three (C3) or six (C6) courses of carboplatin (area under the curve (AUC) 4, Chatelut's formula, equivalent to Calvert's AUC 5) on day 1 and vinorelbine 25 mg m(-2) on days 1 and 8 of a 3-week cycle. Key end points were QoL at 18 weeks, measured with EORTC Quality of Life Questionnaire (QLQ)-C30 and QLQ-LC13, and overall survival. Secondary end points were progression-free survival and need of palliative radiotherapy. Two hundred and ninety-seven patients were randomised (C3 150, C6 147). Their median age was 65 years, 30% had PS 2 and 76% stage IV disease. Seventy-eight and 54% of C3 and C6 patients, respectively, completed all scheduled chemotherapy courses. Compliance with QoL questionnaires was 88%. There were no significant group differences in global QoL, pain or fatigue up to 26 weeks. The dyspnoea palliation rate was lower in the C3 arm at 18 and 26 weeks (P<0.05), but this finding was inconsistent across different methods of analysis. Median survival in the C3 group was 28 vs 32 weeks in the C6 group (P=0.75, HR 1.04, 95% CI 0.82-1.31). One- and 2-year survival rates were 25 and 9% vs 25 and 5% in the C3 and C6 arm, respectively. Median progression-free survival was 16 and 21 weeks in the C3 and C6 groups, respectively (P=0.21, HR 0.86, 95% CI 0.68-1.08). In conclusion, palliative chemotherapy with carboplatin and vinorelbine beyond three courses conveys no survival or consistent QoL benefits in advanced NSCLC.

Figure 1

Mean score changes from baseline to key follow-up time points for primary outcome symptoms and global QoL, calculated from individual patients measured at baseline and 9 weeks (C3, N=105; C6, N=103), 18 weeks (C3, N=77; C6, N=87) and 26 weeks (C3, N=62; C6, N=73), respectively. For symptom measures score, changes >0 indicate increased symptoms (i.e. deterioration), while for the global QoL score, changes >0 indicate improvement. No significant group differences were seen.

Figure 2

Rates of palliation of core symptoms and global QoL, defined as improvement, control or prevention, and death counted as nonpalliation. Numbers of evaluable patients (including deceased) were 256 at 9 weeks (C3 127, C6 129), 270 at 18 weeks (C3 133, C6 137) and 282 at 26 weeks (C3 140, C6 142). ^*P<0.05; ^***P<0.001; χ² test.

Figure 3

Overall survival by treatment group: C3 (randomised to receive three courses) marked with solid line and C6 (randomised to receive six courses) with dotted line. P-value refers to a log-rank test.

Figure 4

Progression-free survival by treatment group: C3 (randomised to receive three courses) marked with solid line and C6 (randomised to receive six courses) with dotted line. P-value refers to a log-rank test.