Jean-Louis Pujol1, Robert Pirker2, Thomas J Lynch3, Charles A Butts4, Rafael Rosell5, Frances A Shepherd6, Johan Vansteenkiste7, Kenneth J O'Byrne8, Barbara de Blas9, Jim Heighway10, Anja von Heydebreck9, Nick Thatcher11. 1. Centre Hospitalier Universitaire de Montpellier, Hôpital Arnaud de Villeneuve, Montpellier, France. Electronic address: jl-pujol@chu-montpellier.fr. 2. Department of Medicine I, Medical University of Vienna, Vienna, Austria. 3. Smilow Cancer Hospital, Yale Cancer Center, New Haven, CT, United States. 4. Cross Cancer Center, Edmonton, Alberta, Canada. 5. Catalan Institute of Oncology, Hospital Germans Trias i Pujol, Badalona, Spain. 6. University Health Network, Princess Margaret Hospital Site, University of Toronto, Toronto, Ontario, Canada. 7. University Hospital Gasthuisberg, KU Leuven, Belgium. 8. St James's Hospital, Dublin, Ireland. 9. Merck KGaA, Darmstadt, Germany. 10. Cancer Communications and Consultancy Ltd., Knutsford, Cheshire, UK. 11. Christie Hospital NHS Trust, Manchester, UK.
Abstract
OBJECTIVES: Four randomized phase II/III trials investigated the addition of cetuximab to platinum-based, first-line chemotherapy in patients with advanced non-small cell lung cancer (NSCLC). A meta-analysis was performed to examine the benefit/risk ratio for the addition of cetuximab to chemotherapy. MATERIALS AND METHODS: The meta-analysis included individual patient efficacy data from 2018 patients and individual patient safety data from 1970 patients comprising respectively the combined intention-to-treat and safety populations of the four trials. The effect of adding cetuximab to chemotherapy was measured by hazard ratios (HRs) obtained using a Cox proportional hazards model and odds ratios calculated by logistic regression. Survival rates at 1 year were calculated. All applied models were stratified by trial. Tests on heterogeneity of treatment effects across the trials and sensitivity analyses were performed for all endpoints. RESULTS: The meta-analysis demonstrated that the addition of cetuximab to chemotherapy significantly improved overall survival (HR 0.88, p=0.009, median 10.3 vs 9.4 months), progression-free survival (HR 0.90, p=0.045, median 4.7 vs 4.5 months) and response (odds ratio 1.46, p<0.001, overall response rate 32.2% vs 24.4%) compared with chemotherapy alone. The safety profile of chemotherapy plus cetuximab in the meta-analysis population was confirmed as manageable. Neither trials nor patient subgroups defined by key baseline characteristics showed significant heterogeneity for any endpoint. CONCLUSION: The addition of cetuximab to platinum-based, first-line chemotherapy for advanced NSCLC significantly improved outcome for all efficacy endpoints with an acceptable safety profile, indicating a favorable benefit/risk ratio.
OBJECTIVES: Four randomized phase II/III trials investigated the addition of cetuximab to platinum-based, first-line chemotherapy in patients with advanced non-small cell lung cancer (NSCLC). A meta-analysis was performed to examine the benefit/risk ratio for the addition of cetuximab to chemotherapy. MATERIALS AND METHODS: The meta-analysis included individual patient efficacy data from 2018 patients and individual patient safety data from 1970 patients comprising respectively the combined intention-to-treat and safety populations of the four trials. The effect of adding cetuximab to chemotherapy was measured by hazard ratios (HRs) obtained using a Cox proportional hazards model and odds ratios calculated by logistic regression. Survival rates at 1 year were calculated. All applied models were stratified by trial. Tests on heterogeneity of treatment effects across the trials and sensitivity analyses were performed for all endpoints. RESULTS: The meta-analysis demonstrated that the addition of cetuximab to chemotherapy significantly improved overall survival (HR 0.88, p=0.009, median 10.3 vs 9.4 months), progression-free survival (HR 0.90, p=0.045, median 4.7 vs 4.5 months) and response (odds ratio 1.46, p<0.001, overall response rate 32.2% vs 24.4%) compared with chemotherapy alone. The safety profile of chemotherapy plus cetuximab in the meta-analysis population was confirmed as manageable. Neither trials nor patient subgroups defined by key baseline characteristics showed significant heterogeneity for any endpoint. CONCLUSION: The addition of cetuximab to platinum-based, first-line chemotherapy for advanced NSCLC significantly improved outcome for all efficacy endpoints with an acceptable safety profile, indicating a favorable benefit/risk ratio.
Authors: Roy S Herbst; Mary W Redman; Edward S Kim; Thomas J Semrad; Lyudmila Bazhenova; Gregory Masters; Kurt Oettel; Perry Guaglianone; Christopher Reynolds; Anand Karnad; Susanne M Arnold; Marileila Varella-Garcia; James Moon; Philip C Mack; Charles D Blanke; Fred R Hirsch; Karen Kelly; David R Gandara Journal: Lancet Oncol Date: 2017-11-20 Impact factor: 41.316