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Trastuzumab in the adjuvant treatment of HER2-positive early breast cancer patients: a meta-analysis of published randomized controlled trials.

Yin W, Jiang Y, Shen Z, Shao Z, Lu J - PLoS ONE (2011)

Bottom Line: The fixed-effects or random-effects model was used to combine data.Furthermore, concomitant use of trastuzumab significantly lowered the hazard of death (P<0.001) but bore a higher incidence of CNS recurrence (P = 0.010), while statistical significance failed to be discerned for either overall survival (P = 0.069) or CNS metastasis (P = 0.374) between the sequential and observation arms.Additionally, our findings indirectly corroborate the superiority of concurrent trastuzumab to sequential use and also illuminate that prolonged survival is the possible reason for the higher incidence of CNS with trastuzumab versus observation.

View Article: PubMed Central - PubMed

Affiliation: Department of Breast Surgery, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.

ABSTRACT

Background: Adjuvant trastuzumab therapy has yielded conflicting results for overall survival, concerns about central nervous system (CNS) metastasis, and questions about optimal schedule. Therefore, we carried out a meta-analysis to assess the benefits of concurrent or sequential trastuzumab with adjuvant chemotherapy for early breast cancer patients with HER2-positive tumors.

Methods: Computerized and manual searches were performed to identify randomized clinical trials comparing adjuvant chemotherapy with or without trastuzumab in HER2-positive early breast cancer patients. Odds ratios were used to estimate the association between the addition of trastuzumab to adjuvant chemotherapy and various survival outcomes. The fixed-effects or random-effects model was used to combine data.

Findings: With six eligible studies identified, this analysis demonstrated that patients with HER2-positive breast cancer derived benefit in disease-free survival, overall survival, locoregional recurrence and distant recurrence (all P<0.001) from the addition of trastuzumab to adjuvant chemotherapy, whereas trastuzumab did worse in CNS recurrence as compared to the control group (P = 0.018). Furthermore, concomitant use of trastuzumab significantly lowered the hazard of death (P<0.001) but bore a higher incidence of CNS recurrence (P = 0.010), while statistical significance failed to be discerned for either overall survival (P = 0.069) or CNS metastasis (P = 0.374) between the sequential and observation arms.

Conclusion: This analysis verifies the efficacy of trastuzumab in the adjuvant setting. Additionally, our findings indirectly corroborate the superiority of concurrent trastuzumab to sequential use and also illuminate that prolonged survival is the possible reason for the higher incidence of CNS with trastuzumab versus observation.

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Related in: MedlinePlus

Sensitivity analyses for the influence of individual studies on the summary OR for the association between trastuzumab administration and DFS (including the DCarboT arm of the BCIRG 006 trial).The vertical midline indicates the overall OR and the lateral vertical lines indicate its 95% CI. Every hollow round indicates the pooled OR when the left study is omitted in this meta-analysis. The two ends of every dotted line represent the respective 95% CI.
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pone-0021030-g004: Sensitivity analyses for the influence of individual studies on the summary OR for the association between trastuzumab administration and DFS (including the DCarboT arm of the BCIRG 006 trial).The vertical midline indicates the overall OR and the lateral vertical lines indicate its 95% CI. Every hollow round indicates the pooled OR when the left study is omitted in this meta-analysis. The two ends of every dotted line represent the respective 95% CI.

Mentions: The sensitivity analyses clarified that no individual study affected the overall OR for DFS regardless of whether the DCarboT arm was included or not, since omission of any single study made no material difference (Figure 4 and Figure S10). The same conclusions were drawn with respect of overall survival, time to locoregional recurrence, time to distant recurrence, time to contralateral breast cancer and time to CNS recurrence (figures not shown).


Trastuzumab in the adjuvant treatment of HER2-positive early breast cancer patients: a meta-analysis of published randomized controlled trials.

Yin W, Jiang Y, Shen Z, Shao Z, Lu J - PLoS ONE (2011)

Sensitivity analyses for the influence of individual studies on the summary OR for the association between trastuzumab administration and DFS (including the DCarboT arm of the BCIRG 006 trial).The vertical midline indicates the overall OR and the lateral vertical lines indicate its 95% CI. Every hollow round indicates the pooled OR when the left study is omitted in this meta-analysis. The two ends of every dotted line represent the respective 95% CI.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3111470&req=5

pone-0021030-g004: Sensitivity analyses for the influence of individual studies on the summary OR for the association between trastuzumab administration and DFS (including the DCarboT arm of the BCIRG 006 trial).The vertical midline indicates the overall OR and the lateral vertical lines indicate its 95% CI. Every hollow round indicates the pooled OR when the left study is omitted in this meta-analysis. The two ends of every dotted line represent the respective 95% CI.
Mentions: The sensitivity analyses clarified that no individual study affected the overall OR for DFS regardless of whether the DCarboT arm was included or not, since omission of any single study made no material difference (Figure 4 and Figure S10). The same conclusions were drawn with respect of overall survival, time to locoregional recurrence, time to distant recurrence, time to contralateral breast cancer and time to CNS recurrence (figures not shown).

Bottom Line: The fixed-effects or random-effects model was used to combine data.Furthermore, concomitant use of trastuzumab significantly lowered the hazard of death (P<0.001) but bore a higher incidence of CNS recurrence (P = 0.010), while statistical significance failed to be discerned for either overall survival (P = 0.069) or CNS metastasis (P = 0.374) between the sequential and observation arms.Additionally, our findings indirectly corroborate the superiority of concurrent trastuzumab to sequential use and also illuminate that prolonged survival is the possible reason for the higher incidence of CNS with trastuzumab versus observation.

View Article: PubMed Central - PubMed

Affiliation: Department of Breast Surgery, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.

ABSTRACT

Background: Adjuvant trastuzumab therapy has yielded conflicting results for overall survival, concerns about central nervous system (CNS) metastasis, and questions about optimal schedule. Therefore, we carried out a meta-analysis to assess the benefits of concurrent or sequential trastuzumab with adjuvant chemotherapy for early breast cancer patients with HER2-positive tumors.

Methods: Computerized and manual searches were performed to identify randomized clinical trials comparing adjuvant chemotherapy with or without trastuzumab in HER2-positive early breast cancer patients. Odds ratios were used to estimate the association between the addition of trastuzumab to adjuvant chemotherapy and various survival outcomes. The fixed-effects or random-effects model was used to combine data.

Findings: With six eligible studies identified, this analysis demonstrated that patients with HER2-positive breast cancer derived benefit in disease-free survival, overall survival, locoregional recurrence and distant recurrence (all P<0.001) from the addition of trastuzumab to adjuvant chemotherapy, whereas trastuzumab did worse in CNS recurrence as compared to the control group (P = 0.018). Furthermore, concomitant use of trastuzumab significantly lowered the hazard of death (P<0.001) but bore a higher incidence of CNS recurrence (P = 0.010), while statistical significance failed to be discerned for either overall survival (P = 0.069) or CNS metastasis (P = 0.374) between the sequential and observation arms.

Conclusion: This analysis verifies the efficacy of trastuzumab in the adjuvant setting. Additionally, our findings indirectly corroborate the superiority of concurrent trastuzumab to sequential use and also illuminate that prolonged survival is the possible reason for the higher incidence of CNS with trastuzumab versus observation.

Show MeSH
Related in: MedlinePlus