MAYBE MORE IS BETTER

Duration of Chemotherapy for Advanced Non–Small-Cell Lung Cancer: A Systematic Review and Meta-Analysis of Randomized Trials

Yu Yang Soon, Martin R. Stockler, Lisa M. Askie, Michael J. Boyer

From the Sydney Cancer Center, Royal Prince Alfred Hospital; National Health and Medical Research Council Clinical Trials Centre, University of Sydney, Sydney, New South Wales, Australia.

Corresponding author: Michael J. Boyer, MB BS, Sydney Cancer Center, Royal Prince Alfred Hospital, Missenden Rd, Camperdown 2050, Sydney, New South Wales, Australia; e-mail: michael.boyer@sswahs.nsw.gov.au.

Purpose To determine if it is preferable to extend chemotherapy beyond a standard number of cycles in patients receiving first-line chemotherapy for advanced non–small-cell lung cancer.

Methods We searched biomedical literature databases and conference proceedings for randomized controlled trials (RCTs) comparing a defined number of cycles with continuation of the same chemotherapy until disease progression, a larger defined number of cycles of identical chemotherapy, and a defined number of cycles of identical initial chemotherapy followed by additional cycles of an alternative chemotherapy. Meta-analysis was performed using the fixed effect model. The primary outcome was overall survival (OS); secondary outcomes included progression-free survival (PFS), adverse events (AE), and health-related quality of life (HRQL).

Results We found 13 RCTs including 3,027 patients. Extending chemotherapy improved PFS substantially (hazard ratio [HR], 0.75; 95% CI, 0.69 to 0.81; P < .00001) and OS modestly (HR, 0.92; 95% CI, 0.86 to 0.99; P = .03). Subgroup analysis revealed that effects on PFS were greater for trials extending chemotherapy with third-generation regimens rather than older regimens (HR, 0.70 interaction v 0.92 interaction; P = .003). Extending chemotherapy was associated with more frequent AE in all trials where it was reported and impaired HRQL in two of seven trials.

Conclusion Extending chemotherapy, particularly with a third-generation regimen, improved PFS substantially, but OS less so. Future trials should test extending treatment with more effective and/or better-tolerated agents.