PURPOSE: Doublet chemotherapy is more effective than single-agent as first-line treatment of advanced non-small-cell lung cancer (NSCLC). As second-line treatment, several randomized trials have been performed comparing single-agent with doublet chemotherapy, but each trial had an insufficient power to detect potentially relevant differences in survival. METHODS: We performed meta-analysis of individual patient data from randomized trials, both published and unpublished, comparing single-agent with doublet chemotherapy as second-line treatment of advanced NSCLC. Primary end point was overall survival (OS). All statistical analyses were stratified by trial. RESULTS: Eight eligible trials were identified. Data of two trials were not available, and data of six trials (847 patients) were collected. Median age was 61 years. Performance status was 0 or 1 in 90%; 80% of patients had received previous platin-based chemotherapy. OS was not significantly different between arms (P = .32). Median OS was 37.3 and 34.7 weeks in the doublet and single-agent arms, respectively. Hazard ratio (HR) was 0.92 (95% CI, 0.79 to 1.08). Response rate was 15.1% with doublet and 7.3% with single-agent (P = .0004). Median progression-free survival was 14 weeks for doublet and 11.7 weeks for single agent (P = .0009; HR, 0.79; 95% CI, 0.68 to 0.91). There was no significant heterogeneity among trials for the three efficacy outcomes. Patients treated with doublet chemotherapy had significantly more grade 3 to 4 hematologic (41% v 25%; P < .0001) and grade 3 to 4 nonhematologic toxicity (28% v 22%; P = .034). CONCLUSION: Doublet chemotherapy as second-line treatment of advanced NSCLC significantly increases response rate and progression-free survival, but is more toxic and does not improve overall survival compared to single-agent.
PURPOSE: Doublet chemotherapy is more effective than single-agent as first-line treatment of advanced non-small-cell lung cancer (NSCLC). As second-line treatment, several randomized trials have been performed comparing single-agent with doublet chemotherapy, but each trial had an insufficient power to detect potentially relevant differences in survival. METHODS: We performed meta-analysis of individual patient data from randomized trials, both published and unpublished, comparing single-agent with doublet chemotherapy as second-line treatment of advanced NSCLC. Primary end point was overall survival (OS). All statistical analyses were stratified by trial. RESULTS: Eight eligible trials were identified. Data of two trials were not available, and data of six trials (847 patients) were collected. Median age was 61 years. Performance status was 0 or 1 in 90%; 80% of patients had received previous platin-based chemotherapy. OS was not significantly different between arms (P = .32). Median OS was 37.3 and 34.7 weeks in the doublet and single-agent arms, respectively. Hazard ratio (HR) was 0.92 (95% CI, 0.79 to 1.08). Response rate was 15.1% with doublet and 7.3% with single-agent (P = .0004). Median progression-free survival was 14 weeks for doublet and 11.7 weeks for single agent (P = .0009; HR, 0.79; 95% CI, 0.68 to 0.91). There was no significant heterogeneity among trials for the three efficacy outcomes. Patients treated with doublet chemotherapy had significantly more grade 3 to 4 hematologic (41% v 25%; P < .0001) and grade 3 to 4 nonhematologic toxicity (28% v 22%; P = .034). CONCLUSION: Doublet chemotherapy as second-line treatment of advanced NSCLC significantly increases response rate and progression-free survival, but is more toxic and does not improve overall survival compared to single-agent.
Authors: Eunice L Kwak; Yung-Jue Bang; D Ross Camidge; Alice T Shaw; Benjamin Solomon; Robert G Maki; Sai-Hong I Ou; Bruce J Dezube; Pasi A Jänne; Daniel B Costa; Marileila Varella-Garcia; Woo-Ho Kim; Thomas J Lynch; Panos Fidias; Hannah Stubbs; Jeffrey A Engelman; Lecia V Sequist; WeiWei Tan; Leena Gandhi; Mari Mino-Kenudson; Greg C Wei; S Martin Shreeve; Mark J Ratain; Jeffrey Settleman; James G Christensen; Daniel A Haber; Keith Wilner; Ravi Salgia; Geoffrey I Shapiro; Jeffrey W Clark; A John Iafrate Journal: N Engl J Med Date: 2010-10-28 Impact factor: 91.245
Authors: N Kentepozidis; P Economopoulou; Ch Christofyllakis; L Chelis; A Polyzos; N Vardakis; F Koinis; L Vamvakas; P Katsaounis; K Kalbakis; Ch Nikolaou; V Georgoulias; A Kotsakis Journal: Clin Transl Oncol Date: 2016-08-04 Impact factor: 3.405
Authors: Gregory A Masters; Sarah Temin; Christopher G Azzoli; Giuseppe Giaccone; Sherman Baker; Julie R Brahmer; Peter M Ellis; Ajeet Gajra; Nancy Rackear; Joan H Schiller; Thomas J Smith; John R Strawn; David Trent; David H Johnson Journal: J Clin Oncol Date: 2015-08-31 Impact factor: 44.544