This special “annual highlights” supplement to Oncology News International is acompilation of major advances in the management of lung cancer during 2003, asreported in ONI. Guest editor Dr. Roy Herbst comments on the reports includedherein and discusses advances in the clinical management of lung cancer, with afocus on developments in targeted therapy, new combinations, adjuvant therapy,induction therapy, and what to watch for in 2004.
VANCOUVER, Canada-In ameta-analysis of 13 randomized trialsin patients with non-small-cell lungcancer (NSCLC), platinum-based regimenscontaining gemcitabine(Gemzar) offered a statistically significantimprovement in overall survivaland progression-free survival, comparedwith other platinum-based regimens.Joan Schiller, MD, professor ofmedicine, University of Wisconsin,Madison, presented the results at the10th World Conference on Lung Cancer(abstract O-239) on behalf of theinternational team of investigators."The gemcitabine-containing regimenswere clearly more effective thanolder regimens containing first- orsecond-generation chemotherapyagents, and at least as effective as thosewith other third-generation agents,"Dr. Schiller said.Guidelines issued in 1997 by theAmerican Society of Clinical Oncology(ASCO) recommended a platinumbasedregimen as optimal therapy inadvanced NSCLC. But there has beenno statistically significant survival benefitshown for any third-generationplatinum-based regimen, althoughgemcitabine/cisplatin (Platinol)showed a small advantage in terms oftime to progression in ECOG 1594,which compared four regimens, shenoted.Meta-Analysisof 13 TrialsThe study reported at the Vancouvermeeting was a meta-analysis of 13 trialsin which gemcitabine plus cisplatin orcarboplatin (Paraplatin) was comparedwith other platinum-based regimens inthe first-line treatment of stage IIIB/IVNSCLC. It was compiled through a comprehensivesearch of published andunpublished sources of all studies reportedby December 2002.A pooled hazard ratio was producedusing a fixed-effects meta-analysis. Statisticalheterogeneity was addressedwith a random-effects model when appropriate.An estimate of absolutetreatment benefit at 1 year was alsoconstructed.Dr. Schiller noted that heterogeneityof multiple studies constitutes apotential weakness of any meta-analysis,but she added that meta-analysisalso offers the strength of statisticalpower and the ability to generate aprecise estimate of treatment effect.This particular meta-analysis was ableto show advantages for gemcitabineplus a platinum agent that smaller studiescould not detect, she said.Thirteen eligible studies generateda pool of 4,556 patients in an analysisof 17 comparators: 12 against platinum-based doublets, including vinorelbine(Navelbine)/cisplatin (6),paclitaxel/cisplatin (2), paclitaxel/carboplatin(2), docetaxel (Taxotere)/cisplatin(1), and etoposide/cisplatin (1).Five studies included single-agent ortriplet-agent regimens, including mitomycin(Mutamycin)/cisplatin/vinorelbineor mitomycin/ifosfamide(Ifex)/cisplatin (4) and cisplatin (1).Benefit forGemcitabine ArmsFor overall survival, a slight butstatistically significant reduction inmortality in favor of the gemcitabinebasedarms was observed, with a hazardratio of 0.90. One-year survivalincreased from approximately 35% to39%, for an absolute survival differenceof 3.9% favoring gemcitabine.Two-year survival rose from 11.6% to14.2% with gemcitabine plus a platinum,Dr. Schiller reported.For progression-free survival aswell, there was a significant improvementreported with the gemcitabine -containing regimens, with a hazardratio of 0.87 and an absolute benefit at1 year of 4.2%.The same trend emerged in separateanalyses of older regimens andregimens containing third-generationagents. The hazard ratios were 0.89 foroverall survival and 0.85 for progression-free survival favoring gemcitabinearms vs older agents, and 0.93and 0.84, respectively, vs other thirdgenerationagents. "Altogether, six ofeight trials of newer agents favoredgemcitabine," Dr. Schiller said.The findings, she added, were upheldin a sensitivity analysis in whichall single or triplet comparator armswere excluded, with hazard ratios of0.92 for overall survival and 0.88 forprogression-free survival.