Neoadjuvant treatment with docetaxel plus lapatinib, trastuzumab, or both followed by an anthracycline-based chemotherapy in HER2-positive breast cancer: results of the randomised phase II EORTC 10054 study

Bonnefoi, Hervé; Jacot, William; Saghatchian, Mahasti; Moldovan, Cosmin; Venat-Bouvet, Laurence; Zaman, Khalil; Matos, Erika; Petit, Thierry; Bodmer, Alexandre; Quénel-Tueux, Nathalie; Chakiba, Camille; Vuylsteke, Peter; Jérusalem, Guy; Brain, Étienne; Trédan, Olivier; Messina, Carlo; Slaets, Leen; Cameron, David

doi:10.1093/annonc/mdu551

Cited by 72 publications

(88 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In addition to NeoALTTO 28 , other neoadjuvant studies have investigated the addition of lapatinib to trastuzumab for the treatment of patients with HER2-positive breast cancer 42, 55, 65 . The Cancer and Leukemia Group B 40601 trial (CALGB 40601) 42 quantified the pCR rates of patients who received weekly paclitaxel and either trastuzumab plus lapatinib or trastuzumab alone; the pCR rate was modestly higher with combined dual-agent HER2 blockade, but this difference did not reach statistical significance: 51% (95% CI 42–60) versus 40% (95% CI 32–49), P = 0.11).…”

Section: Pcr As a Surrogate For Survivalmentioning

confidence: 99%

“…The authors also analysed the results according to gene-expression-based intrinsic molecular subtypes, and gene sequence and copy-number abnormalities in primary tumours and residual disease; these studies revealed that pCR rates were higher among the patients with a specific molecular disease subtype defined as ‘HER2-enriched’ 42, 66 . In addition, the National Surgical Adjuvant Breast and Bowel Project (NSABP) B-41 trial 55 and European Organisation for Research and Treatment of Cancer (EORTC) 10054 trial 65 randomly assigned patients to receive neoadjuvant chemotherapy with either trastuzumab, lapatinib, or the combination of both anti-HER2 agents. The dual-agent HER2-targeted therapy was associated with numerically higher, but not statistically significant, pCR rates than single-agent HER2-directed therapy in both trials 55,65 .…”

Section: Pcr As a Surrogate For Survivalmentioning

confidence: 99%

See 1 more Smart Citation

Translating neoadjuvant therapy into survival benefits: one size does not fit all

et al. 2016

View full text Add to dashboard Cite

Neoadjuvant therapy has been established as an effective therapeutic approach for patients with locally advanced breast cancer. Similar outcomes between neoadjuvant and adjuvant chemotherapy have been demonstrated in several trials. Nevertheless, neoadjuvant therapy has some advantages over adjuvant therapy, including tumour downstaging, in vivo assessment of therapeutic efficacy, reduced treatment durations, and the need to enrol fewer patients for clinical trials to reach their preplanned objectives. The number of neoadjuvant trials in patients with breast cancer has increased substantially in the past 5 years, particularly in the context of HER2-positive disease. Substantial improvements in the pathological complete response rate to anti-HER2 therapy, a proposed surrogate end point for long-term clinical benefit, have been observed with neoadjuvant dual-agent HER2 blockade. Thus, it was hypothesized that this approach would provide additional survival benefits over standard-of-care therapy with the anti-HER2 antibody trastuzumab in the adjuvant setting. Emerging data, however, are calling this notion into question. We discuss potential reasons why results of neoadjuvant trials of targeted therapies have not been mirrored in the adjuvant setting, and other than inherent differences in clinical-trial designs and statistical power, we consider how the biology of the disease, patient characteristics, and drug administration and schedule might influence the results.

show abstract

Section: Pcr As a Surrogate For Survivalmentioning

confidence: 99%

Section: Pcr As a Surrogate For Survivalmentioning

confidence: 99%

Translating neoadjuvant therapy into survival benefits: one size does not fit all

et al. 2016

View full text Add to dashboard Cite

show abstract

“…Some studies are phase II clinical trials for instance TBCRC 006, EORTC 10054, CHER-LOB [67][68][69], the others are phase III clinical trials such as the NOAH trial, NeoALTTO, CALGB 40601, NSABP protocol B-41, the Adjuvant Lapatinib and/or Trastuzumab Treatment Optimization Trial [70][71][72][73]. Such studies have the potential to produce parameters that will inform future modelling exercises.…”

Section: Modellingmentioning

confidence: 99%

A Critical Review of Economic Evaluations of Trastuzumab in the Treatment of Early Stage HER2 Positive Breast Cancer

Nguyen¹,

Nguyen²,

O'Neill³

2017

Pharmacoeconomics

View full text Add to dashboard Cite

Eleven years after Trastuzumab was approved for use in the treatment of early stage human epidermal growth factor receptor positive breast cancer (HER2+) its clinical benefit has been demonstrated in short and long term follow up studies. The cost-effectiveness of the therapy in this context remains the subject of debate with a wide range of Incremental Cost Effectiveness Ratios (ICERs) reported in the literature. While several reviews of the literature have been undertaken these have not provided a critical analysis of the factors that might underlie this heterogeneity. In this review we provide a critical overview of the literature and discuss potential sources of heterogeneity in reported ICERs. We identify gaps in the current literature and provide a rationale for filling these gaps.

show abstract

“…[11] The combination of lapatinib and trastuzumab sequential with chemotherapy has resulted in statistically significant pCR rates. [12,13] In addition, secondary endpoints of event free survival and 3 years overall survival for patient experiencing pCR were superior to the outcomes of patients who did not. [14] The promise of this treatment strategy has faded with the presentation of the ALTTO, which failed to show any survival benefit for the combination in the adjuvant setting.…”

Section: Introductionmentioning

confidence: 99%

A phase II trial of neoadjuvant doxorubicin plus cyclophosphamide followed by lapatinib plus docetaxel sequential with adjuvant trastuzumab for treatment of early HER2 positive breast cancers

Vidal

Vontela

Chen

et al. 2017

JST

View full text Add to dashboard Cite

Background: The use of HER2 targeting therapy has revolutionized the treatment of HER2 positive breast cancers. Here, we investigate whether a sequential approach to dual HER2 blockade of lapatinib followed by trastuzumab will result in improved clinical outcomes. Methods: This was a single institution, open label, single arm, phase II trial in women with HER2 positive breast cancer. Volunteers were treated with sequential neoadjuvant doxorubicin (60 mg/m 2 ) and cyclophosphamide (600 mg/m 2 ) (AC) for 4 cycles followed by docetaxel (100 mg/m 2 ) concurrent with lapatinib (1,250 mg) (TL) daily for 21 days for four cycles before definitive surgery. The primary end point was pathologic complete response (pCR).Results: The study accrued only 21 of the 71 planned patients from 2/28/2007 to 5/25/2010. All patients (100%) experienced down staging. The pCR rate was 41% (7/18). 11 patients had tumor size of T3 or greater, 3 of which experienced pCR and only 1 underwent breast conservation (lumpectomy). The most common hematologic AE (all grades) was anemia 17/21 (81%). There were no incidences of grade 3 or 4 anemia. 10 of 21 (48%) patients experience a non-hematologic grade 3 AE. The most common non-hematologic AEs (all grades) were irregular menses 20/21 (95%) and hand-foot-skin reactions 20/21 (95%). No increase cardiac abnormalities were noted. The DFS at data cut off was 87.5%. Conclusion:The provocative pCR and DFS results in this high risk locally advanced patient population should be viewed with caution given results of the Adjuvant Lapatinib And/Or Trastuzumab Treatment Optimisation study (ALTTO) clinical trial.

show abstract

Neoadjuvant treatment with docetaxel plus lapatinib, trastuzumab, or both followed by an anthracycline-based chemotherapy in HER2-positive breast cancer: results of the randomised phase II EORTC 10054 study

Abstract: NCT00450892.

Cited by 72 publications

References 24 publications

Translating neoadjuvant therapy into survival benefits: one size does not fit all

Translating neoadjuvant therapy into survival benefits: one size does not fit all

A Critical Review of Economic Evaluations of Trastuzumab in the Treatment of Early Stage HER2 Positive Breast Cancer

A phase II trial of neoadjuvant doxorubicin plus cyclophosphamide followed by lapatinib plus docetaxel sequential with adjuvant trastuzumab for treatment of early HER2 positive breast cancers

Contact Info

Product

Resources

About