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Association details:
| Biomarker: | HER-2 positive |
|---|---|
| Cancer: | HER2 Positive Breast Cancer |
| Drug: | Nerlynx (neratinib) (EGFR inhibitor, HER2 inhibitor, HER4 inhibitor) |
| Direction: | Sensitive |
Evidence:
Title:
CANBRIDGE PHARMACEUTICALS RECEIVES MARKETING APPROVAL FOR NERLYNX® (NERATINIB) IN TAIWAN
Published date:
08/07/2020
Excerpt:
BEIJING & SHANGHAI--CANbridge Pharmaceuticals Inc., a biopharmaceutical company developing innovative drug candidates to treat underserved medical conditions, announced that it has received marketing approval from the Taiwan Food and Drug Administration for NERLYNX® (neratinib) for the extended adjuvant treatment of adult patients with early stage HER2-positive breast cancer following adjuvant trastuzumab-based therapy.
Source:
Excerpt:
NERLYNX is a kinase inhibitor indicated:...In combination with capecitabine, for the treatment of adult patients with advanced or metastatic HER2-positive breast cancer who have received two or more prior anti-HER2 based regimens in the metastatic setting.
Secondary therapy:
capecitabine
Source:
Excerpt:
NERLYNX is a kinase inhibitor indicated:...As a single agent, for the extended adjuvant treatment of adult patients with early stage HER2-positive breast cancer, to follow adjuvant trastuzumab-based therapy.
Source:
Title:
Pan-Asian adapted ESMO Clinical Practice Guidelines for the management of patients with early breast cancer: a KSMO-ESMO initiative endorsed by CSCO, ISMPO, JSMO, MOS, SSO and TOS
Published date:
04/01/2020
Excerpt:
The ESMO Magnitude of Clinical Benefit Score (MCBS) for the new therapies pertuzumab and neratinib were added to the recommendations.. Neratinib after trastuzumab-based adjuvant therapy in HER2-positive breast cancer (ExteNET).
DOI:
10.1016/j.annonc.2020.01.008 4
Source:
Title:
Selection of Optimal Adjuvant Chemotherapy and Targeted Therapy for Early Breast Cancer
Published date:
05/22/2018
Excerpt:
Recommendation...Clinicians may use extended adjuvant therapy with neratinib for patients with early-stage, HER2- positive breast cancer.
DOI:
10.1200/JCO.2018.78.8604
Source:
Excerpt:
…HER-2 positive disease, other recommended regimen added: neratinib plus capecitabine as a category 2A option.
Invasive Breast Cancer...PERATIVE/ADJUVANT THERAPY REGIMENS:...HER-2 Positive...Useful in Certain Circumstances: Neratinib
Secondary therapy:
capecitabine
Source:
Title:
Overall survival with neratinib after trastuzumab-based adjuvant therapy in HER2-positive breast cancer (ExteNET): A randomised, double-blind, placebo-controlled, phase 3 trial
Published date:
02/09/2023
Excerpt:
...HER2-positive breast cancer who had completed neoadjuvant and adjuvant chemotherapy plus trastuzumab were eligible. Patients were randomly assigned to oral neratinib... Eight-year overall survival rates were 90.1% (95% CI 88.3-91.6) with neratinib and 90.2% (95% CI 88.4-91.7)...Overall survival in the extended adjuvant setting was comparable for neratinib and placebo after a median follow-up of 8.1 years in women with early-stage HER2-positive breast cancer.
DOI:
10.1016/j.ejca.2023.02.002
Trial ID:
Source:
Title:
Safety and efficacy of monoclonal antibodies and tyrosine kinase inhibitors in advanced breast carcinoma.
Published date:
05/26/2022
Excerpt:
...phase III trials incorporating TKIs such as Neratinib (NER) and Tucatinib (TUC), there was improved OS (21m Vs 18.7, 24.7m Vs 19.2m respectively) as compared to Standard of care and chemotherapy….Both monoclonal antibodies and tyrosine kinase inhibitors show clinically significant benefits in advanced HER2 positive breast carcinoma.
DOI:
10.1200/JCO.2022.40.16_suppl.e13017
Source:
Title:
Analysis of the pan-Asian subgroup of patients in the NALA Trial: a randomized phase III NALA Trial comparing neratinib+capecitabine (N+C) vs lapatinib+capecitabine (L+C) in patients with HER2+metastatic breast cancer (mBC) previously treated with two or more HER2-directed regimens
Published date:
09/23/2021
Excerpt:
NALA was a phase III randomized trial that assessed the efficacy and safety of neratinib+capecitabine (N+C) against lapatinib+capecitabine (L+C) in HER2+ metastatic breast cancer (mBC) patients...Median PFS of N+C and L+C was 7.0 and 5.4 months (P = 0.0011), respectively. Both median OS (23.8 versus 18.7 months; P = 0.185) and DoR (11.1 versus 4.2 months; P < 0.0001) were extended with N+C, compared to L+C.
Secondary therapy:
capecitabine
DOI:
10.1007/s10549-021-06313-5
Trial ID:
Source:
Title:
Efficacy of Neratinib Plus Capecitabine in the Subgroup of Patients with CNS Involvement from the NALA Trial
Published date:
05/24/2021
Excerpt:
NALA was a randomized, active-controlled trial in patients who received two or more previous HER2-directed regimens for HER2-positive MBC....mean PFS through 24 months was 7.8 months with N + C versus 5.5 months with L + C...the combination of neratinib plus capecitabine was associated with improved progression-free survival and CNS outcomes compared with lapatinib plus capecitabine.
Secondary therapy:
capecitabine
DOI:
https://doi.org/10.1002/onco.13830
Trial ID:
Source:
Title:
45P - Long-term Efficacy of Neratinib in HER2-Positive Early-Stage Breast Cancer: Overall Survival and Central Nervous System Outcomes from the Phase 3 ExteNET Trial
Published date:
05/03/2021
Excerpt:
2840 patients were randomized (1420 per group). After a median follow-up of 8.1y, 8y OS rates were 90.1% (95% CI 88.3‒91.6) for neratinib and 90.2% (95% CI 88.4‒91.7) for placebo (absolute difference –0.1%; stratified HR=0.95; 95% CI 0.75‒1.21; p=0.6914). At 5y, cumulative incidence of CNS recurrences was 1.3% (95% CI 0.8–2.1) with neratinib and 1.8% (95% CI 1.2–2.7) with placebo, and CNS-DFS rates were 97.5% (95% CI 96.4–98.3) and 96.4% (95% CI 95.2–97.4), respectively (HR=0.73; 95% CI 0.45–1.17). No new safety signals were reported. Neratinib is the first HER2-directed agent to show a trend towards improved CNS outcomes in HER2+ eBC, providing further support for current NCCN guidelines that recommend neratinib-based therapy for brain metastases from HER2-positive breast cancer.
Trial ID:
Source:
Title:
Neratinib + capecitabine (N+C) vs lapatinib + capecitabine (L+C) in Asians with HER2+ metastatic breast cancer (MBC) previously treated with two or more HER2-directed regimens: A Pan-Asian analysis of the phase III NALA trial
Published date:
11/17/2020
Excerpt:
HER2+ MBC pts were randomized 1:1 to N (240mg qd) + C (750mg/m2 bid, day 1-14) or L (1250mg qd) + C (1000mg/m2 bid, day 1-14) in 21-day cycles....In Asian pts, significant improvement in PFS (median 7.0 vs 5.4 mo, HR=0.58; p<0.001) and overall cumulative incidence of intervention for CNS disease (27.9 vs 33.8%; p=0.039) was observed for N+C vs L+C, and a positive trend in OS was noted (median: 23.8 vs 18.7 mo, HR=0.79; p=0.185).
Secondary therapy:
capecitabine
Trial ID:
Source:
Title:
Impact of neratinib on outcomes in HER2-positive metastatic breast cancer patients with central nervous system disease at baseline: Findings from the phase 3 NALA tria
Published date:
11/17/2020
Excerpt:
NALA was an international, randomized, open-label, active-controlled, phase 3 study in patients with HER2+ MBC who had received ≥2...Regardless of the status of CNS metastases at baseline, patients appeared to have better outcomes in the N+C arm compared with the L+C arm.
Secondary therapy:
capecitabine
Trial ID:
Source:
Title:
Neratinib + capecitabine versus lapatinib + capecitabine in patients with HER2+ metastatic breast cancer previously treated with <2 HER2-directed regimens: Findings from the multinational, randomized, phase III NALA trial.
Published date:
07/22/2020
Excerpt:
621 patients were randomized (307 to N+C; 314 to L+C)....N+C significantly improved PFS with a trend towards improved OS vs L+C. N+C also resulted in a delayed time to intervention for symptomatic CNS disease.
Secondary therapy:
capecitabine
DOI:
10.1200/JCO.2019.37.15_suppl.1002
Trial ID:
Source:
Title:
Neratinib after trastuzumab-based adjuvant therapy in HER2-positive breast cancer (ExteNET): 5-year analysis of a randomised, double-blind, placebo-controlled, phase 3 trial
Published date:
11/13/2017
Excerpt:
After a median follow-up of 5·2 years (IQR 2·1-5·3), patients in the neratinib group had significantly fewer invasive disease-free survival events than those in the placebo group (116 vs 163 events; stratified hazard ratio 0·73, 95% CI 0·57-0·92, p=0·0083).
DOI:
10.1016/S1470-2045(17)30717-9
Trial ID:
Source:
Title:
Neratinib in combination with vinorelbine in metastatic breast cancer patients
Excerpt:
...Confirmed pathologic diagnosis of ErbB-2-positive breast cancer (current stage IV) in female subjects for which vinorelbine plus HKI-272 is a reasonable treatment option (part 2 only).4. ...
Trial ID:
Source:
Title:
An open label phase II study to evaluate neratinib for treatment and prevention of subsequent CNS event(s) in patients with brain metastasis of advanced HER2 positive breast cancer
Excerpt:
...Subjects must meet all of the following criteria in order to be eligible for this study:1) Age ≥ 18 years old2) ECOG performance status ≤ 2 3) Female 4) Diagnosis : histologically or cytologically confirmed HER2-positive tumour status according to the ASCO-CAP guidelines (defined as a 3+ score on immunohistochemistry (IHC) and/or positive by in situ hybridisation (ISH)) with brain metastases, estrogen receptor and progesteron receptor statusCohort 1: with CNS metastases pre-treated with local approaches for the previous CNS events and currently progressive but locally treated CNS metastasis Cohort 2: with a first diagnosis of CNS metastases, asymptomatic or paucisymptomatic not needing immediate local therapy Cohort 3: with confirmed LM defined as the presence of malignant cells in the CSF or combination of typical symptoms and MRI findings5) Specific criteria for cohorts 1 and 2 only: Must have radiologically confirmed metastatic brain lesion by MRI measurable by RANO-BM criteria 6) Specific criteria for cohort 3 only: LM defined as the presence of malignant cells in the CSF or combination of typical symptoms and MRI findings for cohort 37) Subjects should have received at least 1 previous line for the metastatic disease including taxanes based chemotherapy in combination with trastuzumab and pertuzumab (if available) unless contraindicated. ...
Trial ID:
More C2 evidence
Source:
Title:
Neratinib in Treating Older Patients With Stage IV HER2-Positive Breast Cancer
Excerpt:
...- HER2 positivity as defined by American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guidelines...
Trial ID:
Source:
Title:
A Phase 1/2 Study of HKI-272 (Neratinib) in Combination With Paclitaxel (Taxol) in Subjects With Solid Tumors and Breast Cancer
Excerpt:
...- HER2 positive tumor...
Trial ID:
Source:
Title:
A Phase 1/2 Study Of HKI-272 (Neratinib) in Combination With Trastuzumab (Herceptin) In Subjects With Advanced Breast Cancer
Excerpt:
...- HER2 positive breast cancer...
Trial ID:
Source:
Title:
Neratinib adjuvant study
Excerpt:
...Subjects must have histologically confirmed primary adenocarcinoma of the breast that is erbB-2 positive by one of the following assays, performed locally: Fluorescence in Situ Hybridization (FISH) or Silver in Situ Hybridization (SISH), or Chromogenic in Situ Hybridization (CISH), or Immunohistochemistry assay.2. ...
Trial ID:
Source:
Title:
A study before surgery evaluating Regimens with Weekly Paclitaxel plus Neratinib or Trastuzumab or Neratinib and Trastuzumab Followed by Doxorubicin and Cyclophosphamide with Postoperative Trastuzumab in Women with Locally Advanced HER2-Positive Breast Cancer. Studio clinico precedente all'intervento chirurgico per valutare i regimi di Paclitaxel settimanale più Neratinib o Trastuzumab o Neratinib e Trastuzumab seguito da Doxorubicina e Ciclofosfamide con Trastuzumab postoperatorio in donne con tumore alla mammella HER2-positivo localmente avanzato.
Excerpt:
...Breast cancer must be determined to be HER2-positive prior to randomization. ...
Trial ID:
Source:
Title:
Phase 1/2 Randomized, Open-label, Three Arm Study of Neratinib (HKI-272) vs. Neratinib + Capecitabine vs. Lapatinib + Capecitabine, in Subjects with Solid Tumors and ErbB-2 Positive Metastatic or locally advanced Breast Cancer
Excerpt:
...The primary end-point of this study is to assess the safety and define the maximum tolerated dose of the combination of neratinib with capecitabine in subjects with solid tumors, and to compare the objective response rate (ORR = CR + PR) for subjects with erbB-2 positive breast cancer treated at the MTD of neratinib in combination with capecitabine versus neratinib monotherapy versus lapatinib in combination with capecitabine.`...
Trial ID:
Source:
Title:
A Phase 2 Randomized Open Label Study of Neratinib versus Lapatinib plus Capecitabine for the treatment of ErbB-2 Positive Locally Advanced or Metastatic Breast Cancer
Excerpt:
...The primary endpoint is the comparison of the investigator assessed progression-free survival (PFS) following treatment with single agent neratinib versus lapatinib plus capecitabine in subjects with erbB-2-positive locally advanced or metastatic breast cancer. ...
Trial ID:
Source:
Title:
Evaluating the Efficacy of Neratinib on Live Cell HER2 Signaling Transduction Analysis Positive Triple Negative Breast
Excerpt:
...- Patients with multifocal breast cancer are included as long as none of the tumors are HER2 positive by IHC or FISH and targeted lesion meets current...
Trial ID:
Source:
Title:
Three Antidiarrheal Strategies in HER2+/HR+ Early Breast Cancer Patients Treated With Extended Adjuvant Neratinib
Excerpt:
...Documented HER2-positive disease based on local laboratory determination according to American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) 2018 criteria....
Trial ID:
Source:
Title:
Neratinib Dose Escalation Regimen for HER2 Positive Early Breast Cancer
Excerpt:
...- HER2 positive breast cancer diagnosed histologically is defined as HER2 (3+) by immunohistochemistry or HER2 (2+) with positive FISH test；...
Trial ID:
Source:
Title:
Temsirolimus Plus Neratinib for Patients With Metastatic HER2-Amplified or Triple Negative Breast Cancer
Excerpt:
...Phase II HER2-Positive Cohort with dose escalation...
Trial ID:
Source:
Title:
Study Evaluating Neratinib Plus Paclitaxel VS Trastuzumab Plus Paclitaxel In ErbB-2 Positive Advanced Breast Cancer
Excerpt:
...- ErbB-2 positive locally recurrent or metastatic breast cancer...
Trial ID:
Source:
Title:
Evaluation of Neratinib for Treatment and Prevention of Subsequent CNS Event(s) in Patients With Brain Metastasis of Advanced HER2 Positive Breast Cancer
Excerpt:
...Diagnosis : histologically or cytologically confirmed HER2-positive tumour status according to the ASCO-CAP guidelines (defined as a 3+ score on immunohistochemistry (IHC) and/or positive by in situ hybridisation (ISH)) with brain metastases, estrogen receptor and progesteron receptor status Cohort 1: with CNS metastases pre-treated with local approaches for the previous CNS events and currently progressive but locally treated CNS metastasis Cohort 2: with a first diagnosis of CNS metastases, asymptomatic or paucisymptomatic...
Trial ID:
Source:
Title:
Study Evaluating The Effects Of Neratinib After Adjuvant Trastuzumab In Women With Early Stage Breast Cancer
Excerpt:
...- Stage II through IIIC HER-2/erbB-2 positive breast cancer with node positive disease....
Trial ID:
Source:
Title:
Efficacy and safety of Disitamab Vedotin plus pyrotinib or naratinib in HER2-positive breast cancer patients with brain metastasis
Excerpt:
...1) Patients who can voluntarily sign an informed consent form; 2) Females aged ≥18 years old when signing the informed consent form; 3) ECOG PS physical status score of 0 to 2 points; 4) Histologically confirmed HER2-positive metastatic breast cancer patients; Note: HER2 positivity refers to at least one occurrence of tumor cell immunohistochemical staining intensity of 3+ or confirmed as positive by fluorescence in situ hybridization [FISH] in the pathological testing/re-review of the primary or metastatic lesions conducted by the participating center's pathology department; 5) Brain metastases confirmed by MRI/enhanced CT, with at least one measurable lesion in the brain based on RECIST 1.1 criteria; 6) Expected survival period ≥3 months; 7) Patient types: Cohort A - newly diagnosed brain metastases patients; Cohort B - patients with progression after whole-brain radiotherapy or stereotactic radiosurgery; 8) Left ventricular ejection fraction (LVEF) ≥50%; 9) QT interval corrected by Fridericia formula (QTcF) of 12-lead electrocardiogram: <450ms for males, <470ms for females; 10) The following conditions should be met in the blood routine examination:① Absolute neutrophil count (ANC) ≥1.5×10^9/L, ② Platelet count ≥100×10^9/L, ③ Hemoglobin ≥90g/L, ④ White blood cell count ≥3.0×10^9/L; 11) Liver function meets the following conditions: ① Serum total bilirubin ≤1.5×upper limit of normal (ULN), or ≤3×ULN if there are liver metastases, ② Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) ≤3×ULN, or ≤5×ULN if there are liver metastases; 12) Renal function meets the following conditions: Serum creatinine ≤1.5×ULN or creatinine clearance ≥50mL/min (calculated according to the Cockroft-Gault formula); 13) Female patients who meet the following conditions can participate in this study: ① Infertility; ② Capable of fertility, with a negative blood pregnancy test result within 7 days before the first administration of the investigational drug, not breastfeeding, and adopting effective contraceptive measures during the screening period, throughout the study, and within 6 months after the last administration of the study drug....
Trial ID:
Source:
Title:
Phase II study to evaluate diarrhoea discontinuations at 3 cycles in patients with early-stage HER2 positive, hormone receptor positive breast cancer treated with neratinib plus loperamide versus neratinib dose escalation plus loperamide administered as needed versus neratinib plus loperamide plus colesevelam Estudio fase II para evaluar la incidencia de abandono debida a diarrea en 3 ciclos de tratamiento en pacientes con cáncer de mama estadio temprano HER2 positivo, receptor hormonal positivo tratados con neratinib más loperamida frente a neratinib con escalada de dosis más loperamida administrada solamente según necesidad frente a neratinib más loperamida más colesevelam
Excerpt:
...- Histologically confirmed Stage IB through Stage IIIC primary adenocarcinoma of the breast.- Documented HER2-positive disease based on local laboratory determination according to ASCO/CAP 2018 criteria. ...
Trial ID:
Less C2 evidence
Source:
Title:
Neratinib in advanced HER2-positive breast cancer: experience from the royal Marsden hospital
Published date:
08/17/2022
Excerpt:
To describe the tolerability and efficacy of neratinib as a monotherapy and in combination with capecitabine in advanced HER2-positive breast cancer...After a median duration of follow-up of 38.5 months, the median PFS for all patients was 5.9 months (95% confidence interval (CI) 4.9-7.4 months) and median OS was 15.0 months (95% Cl 10.4-22.2 months). Amongst the 52.7% (38/72) patients with confirmed brain metastases at baseline, median PFS was 5.7 months (95% CI 2.9-7.4 months) and median OS was 12.5 months (95% CI 7.7-21.4 months)....Neratinib monotherapy or in combination with capecitabine is a useful treatment for patients with and without brain metastases.
Secondary therapy:
capecitabine
DOI:
10.1007/s10549-022-06703-3
Source:
Title:
Neratinib and Capecitabine for the Treatment of Leptomeningeal Metastases from HER2-Positive Breast Cancer: A Series in the Setting of a Compassionate Program
Published date:
02/25/2022
Excerpt:
This study has evaluated the activity of neratinib in association with capecitabine in 10 patients with LM from HER2-positive BC...The best radiological response was stable disease in 60% of patients....This small series shows that the combination of neratinib and capecitabine is a safe treatment in LM from heavily pretreated HER2-positive BC with clinical efficacy in some patients and is worth investigating in a larger study.
Secondary therapy:
capecitabine
DOI:
10.3390/cancers14051192
Source:
Title:
Phase Ib/II study of capecitabine 7/7 schedule with neratinib in patients with HER2-positive metastatic breast cancer (MBC)
Published date:
05/19/2021
Excerpt:
Neratinib (N)...Capecitabine (X)...We conducted phase Ib/II study of N with X (7/7) with loperamide and colestipol prophylaxis in patients (pts) with pretreated HER2+ MBC (NCT03377387). Twenty-two of 24 pts have been enrolled in phase II. Of 22 pts, data show 6 with partial response, 8 with stable disease, 3 with progressive disease...
Secondary therapy:
capecitabine
DOI:
10.1200/JCO.2021.39.15_suppl.e15016
Trial ID:
Source:
Title:
Neratinib: an option for HER2-positive metastatic breast cancer
Published date:
09/01/2020
Excerpt:
When combined with fulvestrant, neratinib demonstrated efficacy in patients with HER2-positive breast cancer, regardless of their hormone receptor status.
Secondary therapy:
fulvestrant
Source:
Title:
Factors associated with the use of adjuvant neratinib in stage I-III HER2-positive breast cancer.
Published date:
05/28/2020
Excerpt:
A total of 350 patients were identified who received adjuvant T for treatment of stage I-III HER2-positive breast cancer within the inclusion timeframe...Patients receiving adjuvant N were less likely to have had a pathologic complete response (pCR) following neoadjuvant chemotherapy than those who did not receive N (23.1% versus 51.0%, P = 0.008).
DOI:
10.1200/JCO.2020.38.15_suppl.e12517
Source:
Title:
Tolerability of neratinib in older adults with HER2 positive or HER2 mutated metastatic breast cancer.
Published date:
05/28/2020
Excerpt:
Median number of cycles completed was 3 (0-13): 1/25 (4%) pts had a partial response, 11/25 (44%) had stable disease, 12/25 (48%) had progression of disease, and 1/25 (4%) was not evaluable for response. PFS was 2.6 months (95% CI [2.56-5.26]). The median OS was 17.4 months (95% CI [10.3, NA])....Neratinib is safe in older adults with HER2 positive or HER2 mutated MBC.
DOI:
10.1200/JCO.2020.38.15_suppl.e13018
Trial ID:
Source:
Title:
Neratinib-based therapy in patients with metastatic HER2-positive breast cancer from Asia
Published date:
08/21/2019
Excerpt:
A total of 793 patients with HER2-positive MBC were included in the efficacy analysis (Asia: 271 patients; other regions: 522 patients). The overall response rate in patients from Asia was 66.4% (180/271) and the median progression-free survival was 55.6 weeks....Neratinib-based therapy is safe and effective in patients with HER2-positive MBC from Asia.
DOI:
10.2217/fon-2019-0222
Source:
Title:
Melatonin potentiates the cytotoxic effect of Neratinib in HER2 + breast cancer through promoting endocytosis and lysosomal degradation of HER2
Published date:
09/23/2021
Excerpt:
The inhibitory effect of Melatonin on HER2 signaling substantially enhanced the cytotoxic effects of the pan-HER inhibitor Neratinib in HER2+ breast cancer cells. Lastly, we demonstrate that dual inhibition of HER2 by combined use of Melatonin and Neratinib effectively blocked the growth of HER2+ breast tumor xenografts in vivo.
DOI:
10.1038/s41388-021-02015-w
Source:
Title:
Comparative analysis of drug response and gene profiling of HER2-targeted tyrosine kinase inhibitors
Published date:
01/21/2021
Excerpt:
CONTRADICTING EVIDENCE:...The anti-proliferative effects of neratinib, lapatinib, and tucatinib were examined across a panel of 115 cancer cell lines...The MDA-MB-453 cell line was the only HER2+ cell line that had a poor response to each TKI.
DOI:
10.1038/s41416-020-01257-x
