Trial reportBreast cancer research : BCR2019
PIK3CA alterations and benefit with neratinib: analysis from the randomized, double-blind, placebo-controlled, phase III ExteNET trial.
Trial report in Breast cancer research : BCR, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00878709 (A Randomized, Double-Blind, Placebo-Controlled Trial Of Neratinib), which is not on this map. Cited by 15 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
A Randomized, Double-Blind, Placebo-Controlled Trial Of Neratinib (HKI-272) After Trastuzumab In Women With Early-Stage HER-2/Neu Overexpressed/Amplified Breast Cancer
Who cites it
15 citing papers in PubMed, 1 synthesis or guideline pooled it, 28 citations in OpenAlex.
- The Predictive Role ofBioMed research international · 2020Pooled it
- Biomarker Analysis of the Phase III NALA Study of Neratinib + Capecitabine versus Lapatinib + Capecitabine in Patients with Previously Treated Metastatic Breast Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2021Trial
- Impact of somatic PIK3CA mutations on clinical outcomes in HER2-positive breast cancer.Breast cancer research : BCR · 2026Article
- Addition of Ipatasertib to Dual Anti-HER2 Maintenance Therapy in HER2-Positive Metastatic Breast Tumors with PIK3CA Mutations: The Phase Ib SOLTI-1507 IPATHER Trial.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026Article
- Review
- Targeting kinases that regulate programmed cell death: a new therapeutic strategy for breast cancer.Journal of translational medicine · 2025Review
- Size and Treatment Outcomes of HR+, HER2- Early Breast Cancer Population With High Risk of Recurrence: A Real-World Cohort Study With Danish Breast Cancer Cooperative Group Registry Data.Journal of health economics and outcomes research · 2025Article
- Comparison of long-term outcome between clinically high risk lobular versus ductal breast cancer: a propensity score matched study.EClinicalMedicine · 2024Article
- Neratinib for HER2-positive breast cancer with an overlooked option.Molecular medicine (Cambridge, Mass.) · 2023Review
- A scoping review of statistical methods in studies of biomarker-related treatment heterogeneity for breast cancer.BMC medical research methodology · 2023Article
- Individualizing Curative-Intent Therapy in HER2-Positive Early-Stage Breast Cancer.Current treatment options in oncology · 2023Review
- Review
- PIK3CA co-occurring mutations and copy-number gain in hormone receptor positive and HER2 negative breast cancer.NPJ breast cancer · 2022Article
- Article
- Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
26 authors at 20 institutions in 16 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundNeratinib is an irreversible pan-HER tyrosine kinase inhibitor that inhibits PI3K/Akt and MAPK signaling pathways after HER2 receptor activation. The ExteNET study showed that neratinib significantly improved 5-year invasive disease-free survival (iDFS) in women who completed trastuzumab-based adjuvant therapy for early breast cancer (EBC). We assessed the prognostic and predictive significance of PIK3CA alterations in patients in ExteNET.
methodsParticipants were women aged ≥ 18 years (≥ 20 years in Japan) with stage 1-3c (modified to stage 2-3c in February 2010) operable breast cancer, who had completed (neo)adjuvant chemotherapy plus trastuzumab ≤ 2 years before randomization, with no evidence of disease recurrence or metastatic disease at study entry. Patients were randomized to oral neratinib 240 mg/day or placebo for 1 year. Formalin-fixed, paraffin-embedded primary tumor specimens underwent polymerase chain reaction (PCR) PIK3CA testing for two hotspot mutations in exon 9, one hot-spot mutation in exon 20, and fluorescence in situ hybridization (FISH) analysis for PIK3CA amplification. The primary endpoint (iDFS) was tested with log-rank test and hazard ratios (HRs) estimated using Cox proportional-hazards models.
resultsAmong the intent-to-treat population (n = 2840), tumor specimens were available for PCR testing (991 patients) and PIK3CA FISH (702 patients). Overall, 262 samples were PIK3CA altered: 201 were mutated (77%), 52 (20%) were amplified, and 9 (3%) were mutated and amplified. iDFS was non-significantly worse in placebo-treated patients with altered vs wild-type PIK3CA (HR 1.34; 95% CI 0.72-2.50; P = 0.357). Neratinib's effect over placebo was significant in patients with PIK3CA-altered tumors (HR 0.41; 95% CI 0.17-0.90, P = 0.028) but not PIK3CA wild-type tumors (HR 0.72; 95% CI 0.36-1.41; P = 0.34). The interaction test was non-significant (P = 0.309).
conclusionsAlthough there was a greater absolute risk reduction associated with neratinib treatment of patients with PIK3CA-altered tumors in ExteNET, current data do not support PIK3CA alteration as a predictive biomarker of response to neratinib in HER2-positive EBC.
trial registrationClinicalTrials.gov , NCT00878709 . Trial registered April 9, 2009.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.