Do all patients with HER2-positive breast cancer require one year of adjuvant trastuzumab?: A systematic review and meta-analysis.

Stewart, Paul; Blanchette, Phillip; Shah, Prakesh S.; Ye, Xiang Y.; Boldt, Gabriel; Fernandes, Ricardo; Vandenberg, Theodore A.; Raphael, Jacques

doi:10.1200/jco.2019.37.15_suppl.522

Cited by 4 publications

(11 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Admittedly, our meta-analysis is not the first to compare short durations vs. 12 months of trastuzumab, and there are at least six similar meta-analyses or systematic reviews so far (26,27,(36)(37)(38)(39). However, these similar studies were found to have some serious limitations.…”

Section: Discussionmentioning

confidence: 96%

“…Firstly, the two studies presented at ASCO 2019 provided only brief abstracts rather than detailed full-text articles, and they may lack some important information (36,37). Secondly, most similar studies compared short durations vs. 12 months of trastuzumab, but we concentrated on 6 months of trastuzumab rather than several different short durations (26,27,(36)(37)(38)(39). There may be substantial bias if 6 months and other different short durations are combined arbitrarily.…”

Section: Discussionmentioning

confidence: 99%

“…Thirdly, brief abstracts of some relevant RCTs were included in similar meta-analyses published before June 2019 (26,27,(36)(37)(38)(39), because the latest results of two key RCTs (15,16) were published in the Lancet journal in June 2019; this may have substantially decreased the reliability of their final outcomes. Fourthly, previous meta-analyses (36)(37)(38)(39) lacked relevant registration information in PROSPERO, which was indispensable for performing meta-analyses. However, our meta-analysis has some irreplaceable advantages compared with previous similar meta-analyses: (1) The detailed full text was provided in our meta-analysis, and ours could supplement some important information compared with the two previous metaanalyses (36,37).…”

Section: Discussionmentioning

confidence: 99%

“…Fourthly, previous meta-analyses (36)(37)(38)(39) lacked relevant registration information in PROSPERO, which was indispensable for performing meta-analyses. However, our meta-analysis has some irreplaceable advantages compared with previous similar meta-analyses: (1) The detailed full text was provided in our meta-analysis, and ours could supplement some important information compared with the two previous metaanalyses (36,37). (2) We only concentrated on 6 months of trastuzumab rather than several different short durations, so our meta-analysis had greater accuracy and possibly less bias than most similar meta-analyses (26,27,(36)(37)(38)(39).…”

Section: Discussionmentioning

confidence: 99%

“…However, our meta-analysis has some irreplaceable advantages compared with previous similar meta-analyses: (1) The detailed full text was provided in our meta-analysis, and ours could supplement some important information compared with the two previous metaanalyses (36,37). (2) We only concentrated on 6 months of trastuzumab rather than several different short durations, so our meta-analysis had greater accuracy and possibly less bias than most similar meta-analyses (26,27,(36)(37)(38)(39). (3) Unlike most similar meta-analyses (26,27,(36)(37)(38)(39), we included the full texts of all relevant RCTs, and we made full use of the full texts and Supplementary Materials of these RCTs.…”

Section: Discussionmentioning

confidence: 99%

See 4 more Smart Citations

Six Months vs. 12 Months of Adjuvant Trastuzumab Among Women With HER2-Positive Early-Stage Breast Cancer: A Meta-Analysis of Randomized Controlled Trials

Deng

Wang

et al. 2020

Front. Oncol.

View full text Add to dashboard Cite

Both 12 and 6 months of trastuzumab in combination with chemotherapy are effective for HER2+ early-stage breast cancer. This meta-analysis was performed to assess the effectiveness and the toxicity of the two durations. Methods and Materials: We acquired relevant randomized controlled trials (RCTs) from PubMed, the Cochrane Library, ScienceDirect, EMBASE, Ovid MEDLINE, Web of Science, Scopus, and Google Scholar. Our endpoints included disease-free survival (DFS), overall survival (OS), number of recurrences, mortality and early stopping of trastuzumab, and adverse events (AEs). Results: We included five good-quality studies. Both durations of trastuzumab were effective among women with HER2+ early-stage breast cancer, but 12 months of trastuzumab appeared to have better DFS [hazard ratio (HR) = 1.10, 95% confidence interval (CI): 0.99-1.23, P = 0.09] and better OS than 6 months of trastuzumab (HR = 1.14, 95% CI: 0.99-1.32, P = 0.07). However, the 12 month group had more AEs, especially cardiac events [risk ratio (RR) = 0.66, 95% CI: 0.56-0.77, P < 0.00001]. In our sub-analyses, the 12 months duration had better DFS among patients using trastuzumab concurrently than the 6 months duration (HR = 1.23, 95% CI: 1.06-1.44, P = 0.006). Additionally, the 12 months duration had superior OS in women with ER-negative breast cancer (HR = 1.51, 95% CI: 1.10-2.08, P = 0.01) and patients treated with trastuzumab concurrently than the 6 months duration (HR = 1.61, 95% CI: 1.13-2.29, P = 0.008). Conclusions: Twelve months was the standard duration of adjuvant trastuzumab among patients with HER2+ early-stage breast cancer, with a tendency toward superior survival. However, patients in the 12 month group had more significant cardiac toxicity than those in the 6 month group.

show abstract

Section: Discussionmentioning

confidence: 96%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 3 more Smart Citations

Six Months vs. 12 Months of Adjuvant Trastuzumab Among Women With HER2-Positive Early-Stage Breast Cancer: A Meta-Analysis of Randomized Controlled Trials

Deng

Wang

et al. 2020

Front. Oncol.

View full text Add to dashboard Cite

show abstract

Cardiotoxicity of trastuzumab given for 12 months compared to shorter treatment periods: a systematic review and meta-analysis of six clinical trials

et al. 2020

View full text Add to dashboard Cite

BackgroundTreatment de-escalation in early-stage, human epidermal growth factor receptor 2 (HER2)-positive breast cancer (BC) has been attempted in order to decrease costs and toxicities. One of the strategies pursued is decreasing trastuzumab treatment duration, with mixed results thus far. Trastuzumab-associated cardiotoxicity, however, may be more frequent with 12 months of trastuzumab compared with shorter treatment lengths. Therefore, we have conducted a meta-analysis to address this question.Materials and methodsA meta-analysis of trials testing 12 months of adjuvant trastuzumab versus shorter regimens, reporting cardiac outcomes in patients with HER2-positive BC was performed with the random effects model with inverse variance weighting.ResultsClinical cardiac dysfunction associated with 12 months of trastuzumab versus shorter trastuzumab regimens, including 11 250 patients, showed a pooled OR (pOR) of 1.90 (95% CI 1.37 to 2.64; p value <0.001; I2=65.7%); in the subgroup comparison of 12 versus 6 months, the pOR was 1.57 (95% CI 1.30 to 1.90; p<0.001; I2=5.7%). pOR for low left ventricular ejection fraction was 1.45 (95% CI 1.19 to 1.75; p<0.001; I2=11.9%), 1.55 (95% CI 1.00 to 2.42; p=0.052; I2=0.0%) for congestive heart failure and 3.70 (95% CI 0.27 to 51.60; p=0.33; I2=78.8%) for premature trastuzumab discontinuation due to cardiotoxicity for 12 months versus shorter trastuzumab regimens. Funnel plot analyses indicated a low risk of publication bias.ConclusionsCompared to shorter treatment durations, there is sufficient evidence that 12 months of trastuzumab yields higher odds for the occurrence of relevant cardiac events. An individual patient-level data meta-analysis is needed in order to provide adequate data on risk factors for cardiotoxicity.

show abstract

Optimum adjuvant trastuzumab duration for human epidermal growth factor receptor-2 positive breast cancer: a network meta-analysis of randomized trials

Ma¹,

Tang²,

Hu³

et al. 2021

Transl Cancer Res TCR

View full text Add to dashboard Cite

Background: Adjuvant trastuzumab treatment for 12 months is the standard-of-care for early HER2positive breast cancer; however, the optimal duration is unclear. We performed a network meta-analysis (NMA) to determine the optimal treatment duration.Methods: We identified 16 randomized controlled trials involving 29,837 patients that assessed trastuzumab treatment in HER2-positive early breast cancer. Our NMA compared six trastuzumab durations: observation, T-9 weeks, T-12 weeks, T-6 months, T-12 months, and T-24 months. We assessed overall survival (OS), disease-free survival (DFS), acceptability, and cardiotoxicities and grade 3-4 nonhematologic toxicities, and ranked the durations in terms of efficacy and safety by surface under the cumulative ranking (SUCRA).Results: Pairwise meta-analysis showed that while T-6 months was associated with a significant reduction in DFS compared to T-12 months. In our NMA, increasing or decreasing durations showed a significant benefit in DFS compared to observation; however, decreasing durations was not associated with a significant reduction in DFS compared with T-12 months, regardless of the lymph node and hormone receptor statuses.SUCRA ordered the optimum durations of trastuzumab treatment based on PFS as T-12 months (95.6%), T-24 months (69.6%), T-6 months (53.2%), T-9 weeks (41.2%), T-12 weeks (34.3%) and observation (6.1%).Conclusions: Escalating trastuzumab treatment beyond T-12 months confers no additional survival benefit but increased risk of cardiotoxicities. Furthermore, de-escalating treatment confers no improvement on OS compared to T-12 months. These data suggest that T-12 months is the most appropriate treatment schedule for HER2-positive early breast cancer.

show abstract

Do all patients with HER2-positive breast cancer require one year of adjuvant trastuzumab?: A systematic review and meta-analysis.

Cited by 4 publications

References 0 publications

Six Months vs. 12 Months of Adjuvant Trastuzumab Among Women With HER2-Positive Early-Stage Breast Cancer: A Meta-Analysis of Randomized Controlled Trials

Six Months vs. 12 Months of Adjuvant Trastuzumab Among Women With HER2-Positive Early-Stage Breast Cancer: A Meta-Analysis of Randomized Controlled Trials

Cardiotoxicity of trastuzumab given for 12 months compared to shorter treatment periods: a systematic review and meta-analysis of six clinical trials

Optimum adjuvant trastuzumab duration for human epidermal growth factor receptor-2 positive breast cancer: a network meta-analysis of randomized trials

Contact Info

Product

Resources

About