Neratinib Plus Paclitaxel vs Trastuzumab Plus Paclitaxel in Previously Untreated Metastatic ERBB2-Positive Breast Cancer

Awada, Ahmad; Colomer, Ramón; Inoue, Kenichi; Bondarenko, Igor; Badwe, Rajendra; Demetriou, Georgia; Lee, Soo‐Chin; Mehta, Ajay; Kim, Sung‐Bae; Bachelot, Thomas; Goswami, Chanchal; Deo, S. V. S.; Bose, Ron; Wong, Alvin; Xu, Feng; Yao, Bin; Bryce, Richard; Carey, Lisa A.

doi:10.1001/jamaoncol.2016.0237

Cited by 296 publications

(249 citation statements)

References 39 publications

(53 reference statements)

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“…In this study, women with previously untreated HER2-positive metastatic breast cancer received either neratinib 240 mg/day (n = 242) or trastuzumab 4 mg/kg then 2 mg/kg weekly (n = 237) combined with paclitaxel 80 mg/m 2 on days 1, 8, and 15 every 28 days. After a median follow-up of 23.0 months, median PFS, the primary study endpoint, was 12.9 months with neratinib-paclitaxel and 12.9 months with trastuzumab-paclitaxel (hazard ratio 1.02, 95% confidence intervals [CI] 0.81-1.27; p=0.894) [69]. There were also no statistically significant differences between treatment groups for three of five secondary efficacy endpoints (i.e.…”

Section: Pharmacokinetics and Metabolismmentioning

confidence: 93%

“…The results from the first of these studies -NEfERT-T -have recently been reported [69] (Table 3). In this study, women with previously untreated HER2-positive metastatic breast cancer received either neratinib 240 mg/day (n = 242) or trastuzumab 4 mg/kg then 2 mg/kg weekly (n = 237) combined with paclitaxel 80 mg/m 2 on days 1, 8, and 15 every 28 days.…”

Section: Pharmacokinetics and Metabolismmentioning

confidence: 99%

“…A notable finding from the NEfERT-T study was that the incidence of symptomatic or progressive central nervous system (CNS) recurrences was significantly lower in the [69]. Both CNS outcomes were prospectively defined secondary endpoints of the study.…”

Section: Pharmacokinetics and Metabolismmentioning

confidence: 99%

“…Lapatinib has already shown very modest efficacy in CNS metastases [84,85] and several signals from recent trials with neratinib suggest it too may be effective in patients with CNS metastases. Most notable are the data from the NEfERT-T trial which showed a significant reduction in the frequency of symptomatic or progressive CNS recurrences, as well as an improvement in the time to CNS events, with neratinib plus paclitaxel compared with trastuzumab plus paclitaxel [69]. NALA also includes a CNS-focused secondary endpoint (i.e.…”

Section: Expert Opinionmentioning

confidence: 99%

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Pharmacodynamics, pharmacokinetics and clinical efficacy of neratinib in HER2-positive breast cancer and breast cancer with HER2 mutations

Kourié

Chaix

Gombos

et al. 2016

Expert Opinion on Drug Metabolism & Toxicology

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The phase III ExteNET trial shows that neratinib improves 2-year invasive disease-free survival after trastuzumab-based adjuvant therapy in early-stage HER2-positive breast cancer, and in particular HER2+/HR+ tumors. Survival data are awaited. The investigational role of neratinib in high-risk patients or conversely in de-escalation dual regimens with other anti-HER2 therapies and without chemotherapy are of interest. Phase II trials show that neratinib has efficacy, either as monotherapy or in combination with other chemotherapeutic or endocrine agents, in patients with HER2-positive metastatic breast cancer and in tumors harboring HER2 mutations. The role of neratinib in therapeutic algorithms of HER2-positive patients, as well as delaying CNS events, awaits the results of ongoing trials such as NALA. Diarrhea, the main toxicity of neratinib, can be effectively managed with early loperamide prophylaxis.

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Section: Pharmacokinetics and Metabolismmentioning

confidence: 93%

Section: Pharmacokinetics and Metabolismmentioning

confidence: 99%

Section: Pharmacokinetics and Metabolismmentioning

confidence: 99%

Section: Expert Opinionmentioning

confidence: 99%

See 2 more Smart Citations

Pharmacodynamics, pharmacokinetics and clinical efficacy of neratinib in HER2-positive breast cancer and breast cancer with HER2 mutations

Kourié

Chaix

Gombos

et al. 2016

Expert Opinion on Drug Metabolism & Toxicology

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“…In this randomized, controlled, open-label trial (NEFERT-T), neratinib plus paclitaxel was not superior to T-paclitaxel in terms of PFS [12.9 months (95%CI=11.1-14.9) and 12.9 months (95%CI=11.1-14.8), respectively (p=0.89)]. However, the incidence of BM was lower (relative risk, 0.48; 95%CI=0.29-0.79; p=0.002) and the time to CNS metastasis was delayed (HR=0.45; 95%CI=0.26-0.78; p=0 .004) in the experimental arm (18).…”

Section: Figure 2 Mri Images With Se T1 After Gadolinium In Axial (Amentioning

confidence: 96%

Impressive Long-term Response with Pertuzumab and Trastuzumab in HER2-positive Breast Cancer with Brain Metastasis

Russillo

Ferretti

Vidiri³

et al. 2018

In Vivo

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Abstract. This is a case report of a 40-yearIn human epidermal growth factor receptor 2 (HER2)-expressing breast cancer (BC) subtype the incidence of brain metastases (BM) after the diagnosis of the primary tumor is between 3.2% and 3.7% and significantly raises (30-50%) in patients who do not receive adjuvant anti-HER2 monoclonal antibody trastuzumab (T) (1, 2).It has been reported that, although T significantly improves the prognosis of patients with HER2-positive advanced BC (3), the overall survival from the time of diagnosis in women with BC and BM (BCBM) is less than 1.2 years (4, 5).Recently, according to the Cleopatra trial, the combination of pertuzumab (P) and T plus docetaxel showed a significant impact on progression-free survival and overall survival in HER2-positive metastatic BC patients (6). Although this trial did not enroll BCBM patients, an exploratory analysis showed that time to BM development as the first site of disease progression and overall survival were significantly prolonged in patients receiving P plus T vs. T alone (respectively, 15 vs. 11.9 months p=0.0049, and 34.4 vs. 26.3 months p=0.11) (7). These findings are one of the main reasons to treat BCBM patients with the dual blockade plus taxanes as a first-line option. This is a case report of a HER2-positive BC woman with BM as a unique site of disease progression. This patient experienced an impressive clinical benefit by anti-HER2 dual blockade. Case ReportOn November 2009, a 40-year old woman presented with a 20×20 mm mass in her left breast, with palpable fixed axillary nodes. A core needle biopsy of the breast tumor revealed an invasive ductal carcinoma and the fine needle aspiration of an axillary node documented metastasis from BC. Total body Computed Tomography (CT scan) showed absence of distant metastases. The clinical stage at diagnosis was cT2N2M0. The immunohistochemical analysis revealed that the tumor expressed estrogen receptor (ER, 50%), but not progesterone receptor (PGR, 0%) and HER2 (0%).She received neo-adjuvant chemotherapy including 4 courses of 3-weekly doxorubicin 60 mg/m 2 plus cyclophosphamide 600 mg/m 2 followed by 4 courses of 3-weekly docetaxel 100 mg/m 2 . A radical mastectomy with axillary node dissection was subsequently performed. The histological examination revealed a pathological partial response with residual ductal infiltrating carcinoma in the left breast and absence of metastases in the axillary nodes (pT1bN0). The biological profile was: ER 55%, PgR 25%, HER2-negative and Ki-67 15%. The patient received antiestrogen treatment with tamoxifen plus triptorelin until

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Patient Experience Captured by Quality-of-Life Measurement in Oncology Clinical Trials

et al. 2020

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IMPORTANCE Quality of life (QoL) is an important consideration in cancer medicine, especially because drugs are becoming more costly and may only result in modest gains in overall survival.However, there has been no descriptive analysis for the points at which QoL is measured in cancer trials.OBJECTIVE To estimate the prevalence of studies that measure QoL at different points and see how many studies measure QoL for the entirety of a patient's life. DESIGN, SETTING, AND PARTICIPANTS This cross-sectional analysis includes all articles ononcology clinical trials in the 3 highest-impact oncology journals, published between July 2015 and June 2018, that reported QoL outcomes. MAIN OUTCOMES AND MEASURESData were abstracted on when QoL was assessed and the characteristics of these studies. RESULTSFor all 149 studies that met inclusion criteria, QoL assessment was high during treatment (104 articles [69.8%]), during follow-up (81 articles [54.4%]), and after the end of the intervention (68 articles [45.6%]). In 5 of the 149 studies (3.4%), QoL was assessed until death, including in only 1 of the 74 studies on metastatic or incurable cancers. Among these 5 studies, only 1 (20%) used a drug intervention, 1 (20%) used a behavioral intervention, and 2 (40%) used a radiation intervention; only 1 of 5 was in the metastatic setting. The number of studies that reported a positive QoL outcome (ie, QoL outcome was more favorable in the intervention group than in the control group) was between 42 of 81 articles (51.9%) and 16 of 28 articles (57.1%) for most QoL assessment points but only 1 of 5 articles (20%) for studies measuring QoL until death. CONCLUSIONS AND RELEVANCEThis study found that most clinical trials assessed QoL during the treatment or intervention and often during a given amount of follow-up but infrequently assessed QoL on disease progression and rarely followed QoL until the end of the patient's life. Most studies reporting QoL until the end of life reported worse QoL outcomes for the intervention group than the control group. Future research and policy recommendations should consider not just short-term QoL outcomes but QoL outcomes throughout the patient's cancer care. Question How often do oncology studies assess quality of life (QoL) throughout a patient's disease course? Findings This cross-sectional analysis of 149 oncology studies published in highimpact medical and oncology journals found that most studies (69.8%) assessed QoL during the intervention, whereas only 3.4% of studies assessed QoL until the time of death. Meaning These findings suggest that many oncology studies only assess QoL during the intervention; future research should consider the long-term outcomes throughout the patient's life.Oncology, and JAMA Oncology. For each of the journals, we searched for the term quality of life on the journal's website, and we limited the search to research articles only. Selected articles needed to (1) be an RCT, (2) have performed the analysis in the originally randomized groups, (3) have evaluated QoL in ...

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Neratinib Plus Paclitaxel vs Trastuzumab Plus Paclitaxel in Previously Untreated Metastatic ERBB2-Positive Breast Cancer

Abstract: clinicaltrials.gov Identifier: NCT00915018.

Cited by 296 publications

References 39 publications

Pharmacodynamics, pharmacokinetics and clinical efficacy of neratinib in HER2-positive breast cancer and breast cancer with HER2 mutations

Pharmacodynamics, pharmacokinetics and clinical efficacy of neratinib in HER2-positive breast cancer and breast cancer with HER2 mutations

Impressive Long-term Response with Pertuzumab and Trastuzumab in HER2-positive Breast Cancer with Brain Metastasis

Patient Experience Captured by Quality-of-Life Measurement in Oncology Clinical Trials

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