Single-agent versus combination chemotherapy in advanced non-small cell lung cancer: a meta-analysis and the Cancer...

Several randomized trials have compared single-agent chemotherapy with combination chemotherapy in advanced non-small cell lung cancer. In general, response rates were higher with combination regimens, but their impact on survival is unclear. We conducted a meta-analysis of 25 trials involving a total of 5,156 patients with advanced non-small cell lung cancer randomized to a single-agent arm versus a combination arm. The results showed that combination chemotherapy produced a nearly twofold increase in response rate and a modestly improved 1-year survival rate compared with single-agent chemotherapy. However, toxicity was significantly increased, with a 3.6-fold increase in treatment-related mortality. In a subset analysis of trials using either a platinum analog or vinorelbine as single agents and as a component of the combination regimen, the difference was no longer statistically significant, suggesting that more active single agents provide similar survival with less toxicity than combination regimens. Based on these results, the Cancer and Leukemia Group B initiated a large randomized trial comparing paclitaxel with paclitaxel + carboplatin in stage IIIB-IV non-small cell lung cancer patients. The trial will be able to detect a 30% difference in survival. An extensive quality of life analysis and a resource utilization comparison will allow estimation of the incremental cost per quality of life-year gained. This trial will be the first in the United States to prospectively collect and analyze such data in a multidisciplinary approach.