Oops, you're using an old version of your browser so some of the features on this page may not be displaying properly.

MINIMAL Requirements: Google Chrome 24+Mozilla Firefox 20+Internet Explorer 11Opera 15–18Apple Safari 7SeaMonkey 2.15-2.23

Mini Oral session

1O - Neratinib + capecitabine vs lapatinib + capecitabine in HER2+ metastatic breast cancer previously treated with ≥2 HER2-directed regimens: Exploratory biomarker analyses from phase III NALA trial


23 May 2020


Mini Oral session


Cristina Saura Manich


Annals of Oncology (2020) 31 (suppl_2): S15-S41. 10.1016/annonc/annonc117


C. Saura Manich1, A. Vivancos2, J. Matito3, H. Wildiers4, A.M. Brufsky5, A.M. Antunes De Melo e Oliveira6, S. Waters7, S.A. Hurvitz8, B. Moy9, S. Kim10, W.J. Gradishar11, G.S. Queiroz12, E. Cronemberger13, J. Bebchuk14, K. Keyvanjah15, A.S. Lalani16, L.D. Eli17, S. Delaloge18

Author affiliations

  • 1 Solti Breast Cancer Research Group, Vall d’Hebron University Hospital, Vall d’Hebron Institute of Oncology, 08035 - Barcelona/ES
  • 2 Medical Oncology, Vall d’Hebron Institute of Oncology, Barcelona/ES
  • 3 Medical Oncology, Vall d'Hebron University Hospital, Barcelona/ES
  • 4 Medical Oncology, University Hospitals Leuven, Leuven/BE
  • 5 Hematology / Oncology, Magee-Womens Hospital of UPMC, Pittsburgh/US
  • 6 Medical Oncology, Vall d’Hebron University Hospital, Vall d’Hebron Institute of Oncology, Barcelona/ES
  • 7 Medical Oncology, Velindre Cancer Centre, Cardiff/GB
  • 8 Hematology / Oncology Clinical Research Unit, University of California at Los Angeles, Los Angeles/US
  • 9 Medical Oncology, Massachusetts General Hospital Cancer Center, Boston/US
  • 10 Medical Oncology, University of Ulsan College of Medicine, Seoul/KR
  • 11 Medical Oncology, Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago/US
  • 12 Medical Oncology, Hospital Araújo Jorge, Goiânia/BR
  • 13 Medical Oncology, Centro Regional Integrado de Oncologia, Fortaleza/BR
  • 14 Biostatistics, Puma Biotechnology Inc., Los Angeles/US
  • 15 Clinical Science And Clinical Pharmacology, Puma Biotechnology Inc., Los Angeles/US
  • 16 Translational Medicine, Puma Biotechnology Inc., Los Angeles/US
  • 17 Translational Medicine And Diagnostics, Puma Biotechnology Inc., Los Angeles/US
  • 18 Medical Oncology, Institut Gustave Roussy, Villejuif/FR


Login to access the resources on OncologyPRO.

Abstract 1O


The irreversible pan-HER tyrosine kinase inhibitor neratinib had a significant progression-free survival (PFS) benefit in NALA (NCT01808573), a randomized, phase 3 trial comparing neratinib + capecitabine (1500 mg, N+C) vs lapatinib + capecitabine (2000 mg, L+C) in 621 patients (pts) with HER2+ (either IHC3+ or IHC2+/FISH+) metastatic breast cancer (MBC) who received ≥2 prior HER2-directed regimens in the metastatic setting. Here we explore biomarker (PIK3CA or ERBB2 mutations, HER2 protein expression) associations with PFS changes.


PIK3CA and ERBB2 mutations were evaluated by next-generation sequencing on either primary (67.4%, 283/420) or metastatic/lymph node samples (32.6%, 137/420) and confirmed by ddPCR pending tissue availability. HER2 protein expression was evaluated by central IHC, H-score, and HERmark. Hazard ratios (95% CI) for subgroups were estimated using unstratified Cox proportional hazards model.


PIK3CA and ERBB2 mutations were detected at incidences of 35.0% (148/420) and 6.2% (26/420), respectively. PIK3CA mutations were associated with decreased PFS (wt vs mut: HR=0.81; 95% CI 0.64–1.02; p=0.077). ERBB2 mutation trended with better PFS, but sample size was limited (wt vs mut: HR=1.68, CI 0.97–3.29, p=0.086). Higher HER2 protein expression was prognostic of increased PFS when treatment arms were grouped (IHC3+ vs 2+: HR=0.67, CI 0.54–0.82, p<0.001; H-score above vs below median HR=0.77, CI 0.63–0.92, p=0.005; HERmark positive vs equivocal or negative HR=0.71, CI 0.52–0.98, p=0.006). Pts whose tumors had higher HER2 protein expression evaluated by any of the three methods appeared to have derived consistent benefit from N+C vs L+C (HER2 IHC3+: HR=0.64, CI 0.51–0.81, p<0.001; H-score ≥median (240): HR=0.54, CI 0.41–0.72, p<0.001; HERmark positive: HR=0.65, CI 0.50– 0.84, p<0.001).


PIK3CA mutations associate with decreased PFS for pts enrolled in the NALA trial. Higher HER2 protein expression associates with increased PFS in the overall study population, and a greater benefit from N+C vs. L+C.

Clinical trial identification


Editorial acknowledgement

Lee Miller, Miller Medical Communications Ltd.

Legal entity responsible for the study

Puma Biotechnology Inc.


Puma Biotechnology Inc.


C. Saura: Advisory/Consultancy: Puma Biotechnology Inc.; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Pfizer; Advisory/Consultancy: Roche; Advisory/Consultancy: Celgene; Advisory/Consultancy: Daiichi Sankyo; Advisory/Consultancy: Eisai; Advisory/Consultancy: Genomic; Advisory/Consultancy: Novartis; Advisory/Consultancy: Pierre Fabre; Advisory/Consultancy: Synthon; Advisory/Consultancy: Piqur Therapeutics; Advisory/Consultancy: Sanofi. A. Vivancos: Advisory/Consultancy: Guardant Health; Advisory/Consultancy: Novartis; Advisory/Consultancy: Bayer. H. Wildiers: Advisory/Consultancy, Travel/Accommodation/Expenses: Roche; Advisory/Consultancy, Travel/Accommodation/Expenses: Pfizer; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Amgen; Advisory/Consultancy: Lilly; Advisory/Consultancy: Novartis; Advisory/Consultancy: AbbVie; Advisory/Consultancy: Vifor Pharma; Advisory/Consultancy: Celldex therapeutics; Advisory/Consultancy: Janssen-CILAG; Advisory/Consultancy: TRM Oncology; Advisory/Consultancy: Puma Biotechnology Inc.; Advisory/Consultancy: ORION corporation. A.M. Brufsky: Advisory/Consultancy: Pfizer; Advisory/Consultancy: Genentech/Roche; Advisory/Consultancy: Agendia; Advisory/Consultancy: Celgene; Advisory/Consultancy: Novartis; Advisory/Consultancy: Bayer; Advisory/Consultancy: Lilly; Advisory/Consultancy: bioTheranostics; Advisory/Consultancy: NanoString Technologies; Advisory/Consultancy: Genomic Health; Advisory/Consultancy: Puma Biotechnology Inc. M. Oliveira: Advisory/Consultancy: Puma Biotechnology Inc.; Advisory/Consultancy: Roche/Genentech; Advisory/Consultancy: GlaxoSmithKline; Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Roche; Travel/Accommodation/Expenses: Pierre-Fabre; Travel/Accommodation/Expenses: Novartis; Travel/Accommodation/Expenses: GP Pharma; Travel/Accommodation/Expenses: Grunenthal. S. Waters: Advisory/Consultancy: Novartis; Advisory/Consultancy: Roche. B. Moy: Honoraria (self): Medscape Education; Spouse/Financial dependant: Motus GI. S-B. Kim: Advisory/Consultancy: Enzychem; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy, Research grant/Funding (institution): Novartis; Advisory/Consultancy: Odonate; Advisory/Consultancy: Beigene; Research grant/Funding (institution): Sanofi-Genzyme; Research grant/Funding (institution): Dongkook. W.J. Gradishar: Advisory/Consultancy: Genentech/Roche. J. Bebchuk: Full/Part-time employment: Puma Biotechnology Inc. K. Keyvanjah: Full/Part-time employment: Puma Biotechnology Inc. A.S. Lalani: Shareholder/Stockholder/Stock options, Full/Part-time employment: Puma Biotechnology Inc. L.D. Eli: Shareholder/Stockholder/Stock options, Full/Part-time employment: Puma Biotechnology Inc. S. Delaloge: Honoraria (self), Advisory/Consultancy, Licensing/Royalties: Pfizer; Honoraria (self), Advisory/Consultancy, Licensing/Royalties: Novartis; Honoraria (self), Advisory/Consultancy, Licensing/Royalties: Puma Biotechnology Inc.; Honoraria (self), Advisory/Consultancy, Licensing/Royalties: AstraZeneca; Honoraria (self), Advisory/Consultancy: Lilly; Advisory/Consultancy: Orion; Honoraria (self), Advisory/Consultancy: Roche. All other authors have declared no conflicts of interest.

This site uses cookies. Some of these cookies are essential, while others help us improve your experience by providing insights into how the site is being used.

For more detailed information on the cookies we use, please check our Privacy Policy.

Customise settings
  • Necessary cookies enable core functionality. The website cannot function properly without these cookies, and you can only disable them by changing your browser preferences.