Limits...
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.

Show MeSH

Related in: MedlinePlus

Forest plots of OR for the association between trastuzumab administration and distant recurrence by the timing of trastuzumab initiation with respect to chemotherapy (including the DCarboT arm of the BCIRG 006 trial).The size of the square box is proportional to the weight that each study contributes in the meta-analysis. The overall estimate and confidence interval are marked by a diamond. Symbols on the right of the solid line indicate OR>1 and symbols on the left of the solid line indicate OR<1. Abbreviations: M-H = Mantel-Haenszel (fixed-effects method); D+L = DerSimonian and Laird (random-effects method).
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC3111470&req=5

pone-0021030-g002: Forest plots of OR for the association between trastuzumab administration and distant recurrence by the timing of trastuzumab initiation with respect to chemotherapy (including the DCarboT arm of the BCIRG 006 trial).The size of the square box is proportional to the weight that each study contributes in the meta-analysis. The overall estimate and confidence interval are marked by a diamond. Symbols on the right of the solid line indicate OR>1 and symbols on the left of the solid line indicate OR<1. Abbreviations: M-H = Mantel-Haenszel (fixed-effects method); D+L = DerSimonian and Laird (random-effects method).

Mentions: Through the fixed-effects model, we found that the addition of trastuzumab to adjuvant chemotherapy elicited a considerable reduction in risk (Table S1) respectively for death from any cause (DCarboT; OR = 0.78, 95% CI 0.69–0.88, P<0.001; Figure 1), locoregional recurrence (OR = 0.53, 95% CI 0.44–0.65, P<0.001; Figure S4) and distant recurrence (DCarboT; OR = 0.62, 95% CI 0.55–0.69, P<0.001; Figure 2) rather than for contralateral breast cancer (OR = 1.11, 95% CI 0.61–2.01, P = 0.737; Figure S6). Furthermore, the exclusion of the DCarboT arm failed to influence the overall results for both overall survival and time to distant recurrence (Figure S3 and Figure S5).


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)

Forest plots of OR for the association between trastuzumab administration and distant recurrence by the timing of trastuzumab initiation with respect to chemotherapy (including the DCarboT arm of the BCIRG 006 trial).The size of the square box is proportional to the weight that each study contributes in the meta-analysis. The overall estimate and confidence interval are marked by a diamond. Symbols on the right of the solid line indicate OR>1 and symbols on the left of the solid line indicate OR<1. Abbreviations: M-H = Mantel-Haenszel (fixed-effects method); D+L = DerSimonian and Laird (random-effects method).
© Copyright Policy
Related In: Results  -  Collection

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

pone-0021030-g002: Forest plots of OR for the association between trastuzumab administration and distant recurrence by the timing of trastuzumab initiation with respect to chemotherapy (including the DCarboT arm of the BCIRG 006 trial).The size of the square box is proportional to the weight that each study contributes in the meta-analysis. The overall estimate and confidence interval are marked by a diamond. Symbols on the right of the solid line indicate OR>1 and symbols on the left of the solid line indicate OR<1. Abbreviations: M-H = Mantel-Haenszel (fixed-effects method); D+L = DerSimonian and Laird (random-effects method).
Mentions: Through the fixed-effects model, we found that the addition of trastuzumab to adjuvant chemotherapy elicited a considerable reduction in risk (Table S1) respectively for death from any cause (DCarboT; OR = 0.78, 95% CI 0.69–0.88, P<0.001; Figure 1), locoregional recurrence (OR = 0.53, 95% CI 0.44–0.65, P<0.001; Figure S4) and distant recurrence (DCarboT; OR = 0.62, 95% CI 0.55–0.69, P<0.001; Figure 2) rather than for contralateral breast cancer (OR = 1.11, 95% CI 0.61–2.01, P = 0.737; Figure S6). Furthermore, the exclusion of the DCarboT arm failed to influence the overall results for both overall survival and time to distant recurrence (Figure S3 and Figure S5).

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