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Campinas, Brazil

Clark O.,Evidencias Consulting | Botrel T.E.A.,Evidencias Consulting | Paladini L.,Evidencias Consulting | Ferreira M.B.A.,Roche Holding AG
Core Evidence | Year: 2014

Objective: To perform a systematic review and meta-analysis of randomized controlled trials that compared the efficacy of targeted therapy to conventional chemotherapy (CT) in patients with metastatic triple-negative breast cancer (TNBC). Methods: Several databases were searched, including Medline, Embase, LILACS, and CENTRAL. The primary end point was progression-free survival (PFS). We performed a meta-analysis of the published data. The results are expressed as hazard ratio (HR) or risk ratio, with their corresponding 95% confidence intervals (95% CIs). Results: The final analysis included twelve trials comprising 2,054 patients with TNBC, which compared conventional CT alone against CT combined with targeted therapy (bevacizumab [Bev], sorafenib [Sor], cetuximab, lapatinib, and iniparib). PFS was superior in previously untreated patients with TNBC who received Bev plus CT compared to CT alone (fixed effect, HR 0.62, 95% CI 0.51-0.75; P<0.00001). Also, PFS was higher in one study that tested Bev plus CT combination in previously treated patients (HR 0.49, 95% CI 0.33-0.74; P=0.0006). Sor plus CT was also tested as first-line and second-line treatments. The pooled data of PFS favored the combination CT plus Sor (fixed effect, HR 0.69, 95% CI 0.49-0.98; P=0.04). Comparisons of iniparib plus CT also had a better PFS than CT alone (fixed effect, HR 0.75, 95% CI 0.62-0.90; P=0.002). Conclusion: Targeted therapy, when associated with conventional CT, demonstrated gains in the PFS of patients with TNBC. © 2014 Clark et al. Source


Botrel T.E.A.,Evidencias Consulting | Clark O.,Evidencias Consulting | Clark L.,Evidencias Consulting | Paladini L.,Evidencias Consulting | And 2 more authors.
Lung Cancer | Year: 2011

Objective: To perform a systematic review and meta-analysis of all randomized controlled trials comparing the efficacy of chemotherapy (CT) plus Bevacizumab (Bev) versus CT alone in previously untreated locally advanced or metastatic non-small cell lung cancer (NSCLC). Methods: Several databases were searched, including MEDLINE, EMBASE, LILACS, and CENTRAL. The endpoints were overall survival (OS), progression-free survival (PFS) and side effects. We performed a meta-analysis (MA) of the published data, using a fixed effects model and an additional random effects model, when applicable. The results of the MA are expressed as hazard ratio (HR) or risk ratio (RR), with their corresponding 95% confidence intervals (CI95%). We analyzed the use of Bev in the doses of 7.5. mg/kg and 15. mg/kg. Results: The final analysis included 4 trials, comprising 2200 patients. The response rate was higher in patients who received the combination of CT plus Bev 7.5mg/kg (RR=0.58; CI95%=0.46-0.74; p<0.00001) and Bev 15mg/kg (RR=0.53; CI95%=0.45-0.63; p<0.00001) with moderate heterogeneity at dose of 15mg/kg (Chi 2=4.30, df=3 (P=0.23); I 2=30%). The PFS length was longer in patients who received CT plus Bev 7.5mg/kg (HR=0.78, CI95%=0.68-0.90; p=0.0005) and Bev 15mg/kg (HR=0.72, CI95%=0.65-0.80; p<0.00001) with moderate heterogeneity (Bev 7.5mg/kg: Chi 2=1.43, df=1 (P=0.23); I 2=30% and Bev 15mg/kg: Chi 2=7.43, df=3 (P=0.06); I 2=60%). Differences in these end points remained in favor of CT plus Bev when made the analysis by random-effects model. Overall survival was longer in patients who received CT plus Bev 15mg/kg (HR=0.89, CI95%=0.80-1.00; p=0.04), with moderate heterogeneity (Chi 2=5.09, df=3 (P=0.17); I 2=41%). The random-effects model analysis for this endpoint did not confirmed the difference seen in the fixed effects model analysis (HR=0.90, CI95%=0.76-1.07; p=0.23). Severe haematologic toxicities (grade>3), neutropenia and febrile neutropenia were more common among the patients that received Bev. Conclusion: The combination of CT plus Bev increased the response rate and progression-free survival of patients with NSCLC. With respect to overall survival the benefits of Bev remains uncertain. © 2011 Elsevier Ireland Ltd. Source

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