title: Identification of early breast cancer patient cohorts who may benefit from lapatinib therapy.
abstract: In resource-constrained environments many patients with human epidermal growth factor receptor 2 (HER2)+ early breast cancer are currently not offered adjuvant anti-HER2 therapy. For patients who might be able to receive the tyrosine kinase inhibitor (TKI) lapatinib (e.g. after patent expiration), it is important to identify subgroups of patients for whom anti-HER2 TKI therapy could be beneficial. To do this, we used data from 2489 patients with centrally confirmed HER2+ disease enrolled in the adjuvant Tykerb Evaluation After Chemotherapy (TEACH) trial, investigating the effect of lapatinib in patients with HER2+ early breast cancer not treated with trastuzumab. We performed subgroup analyses and number-needed-to-treat (NNT) calculations using patient and tumour associated predictors. Hormone receptor negative (HR-) patients on lapatinib had a significantly prolonged disease-free survival (DFS) compared to HR- patients on placebo (hazard ratio 0.64, P=0.003). For patients with HR- disease, starting treatment with lapatinib ≤1 year from diagnosis improved DFS by 12.1% [2.1-22.1] at 2 years and 15.7% [4.1-27.2] at 5 years. Depending on lymph node status and time since diagnosis the NNT for recurrence (at 5 years) was between 5.9 (node positive patients <1 year from diagnosis) and 15.9. These numbers are in range with numbers reported for up-front adjuvant trastuzumab for HR unselected patients (e.g. 15.6 for DFS at 4 years in HERA). In a subgroup analysis of the adjuvant TEACH trial, we show that anti-HER2 monotherapy with a TKI is beneficial as adjuvant therapy in a subgroup of patients. NNT in HER2+ HR- patients are in range with those reported from up-front adjuvant trastuzumab trials.
authors.affiliation: Center for Oncology and Hematology, Wilhelminen Hospital, Vienna, Austria. Electronic address: kathrin.strasserweippl@gmail.com.
authors.forename: Kathrin
authors.initials: K
authors.lastname: Strasser-Weippl
authors.affiliation: Massachusetts General Hospital Biostatistics Center, Boston, MA, USA. Electronic address: nhorick@partners.org.
authors.forename: Nora
authors.initials: N
authors.lastname: Horick
authors.affiliation: Royal Marsden Hospital, London, UK. Electronic address: ian.smith@rmh.nhs.uk.
authors.forename: Ian E
authors.initials: IE
authors.lastname: Smith
authors.affiliation: Baylor Sammons Cancer Center, Texas Oncology, US Oncology, Dallas, TX, USA. Electronic address: Joyce.OShaughnessy@usoncology.com.
authors.forename: Joyce
authors.initials: J
authors.lastname: O'Shaughnessy
authors.affiliation: Rigshospitalet, DBCG Secretariat, Copenhagen, Denmark. Electronic address: ejlertsen@dadlnet.dk.
authors.forename: Bent
authors.initials: B
authors.lastname: Ejlertsen
authors.affiliation: Mater Hospital, North Sydney, NSW, Australia. Electronic address: franb@bigpond.net.au.
authors.forename: Frances
authors.initials: F
authors.lastname: Boyle
authors.affiliation: University of Texas MD Anderson Cancer Center, Houston, TX, USA. Electronic address: abuzdar@mdanderson.org.
authors.forename: Aman U
authors.initials: AU
authors.lastname: Buzdar
authors.affiliation: Centre GF Leclerc, Dijon, France. Electronic address: pfumoleau@cgfl.fr.
authors.forename: Pierre
authors.initials: P
authors.lastname: Fumoleau
authors.affiliation: Northwestern University, Chicago, IL, USA. Electronic address: WGradishar@nmff.org.
authors.forename: William
authors.initials: W
authors.lastname: Gradishar
authors.affiliation: Hospital Universitario Gregorio Marañón, Universidad Complutense, Madrid, Spain. Electronic address: mmartin@geicam.org.
authors.forename: Miguel
authors.initials: M
authors.lastname: Martin
authors.affiliation: Massachusetts General Hospital, Boston, MA, USA. Electronic address: bmoy@partners.org.
authors.forename: Beverly
authors.initials: B
authors.lastname: Moy
authors.affiliation: Institut Jules Bordet, Université Libre de Bruxelles, Brussels, Belgium. Electronic address: martine.piccart@bordet.be.
authors.forename: Martine
authors.initials: M
authors.lastname: Piccart-Gebhart
authors.affiliation: Sunnybrook Odette Cancer Centre, University of Toronto, Toronto, ON, Canada. Electronic address: kathy.pritchard@sunnybrook.ca.
authors.forename: Kathleen I
authors.initials: KI
authors.lastname: Pritchard
authors.affiliation: Arizona Oncology, US Oncology, Sedona, AZ, USA. Electronic address: deborah.lindquist@usoncology.com.
authors.forename: Deborah
authors.initials: D
authors.lastname: Lindquist
authors.affiliation: GlaxoSmithKline, Collegeville, PA, USA. Electronic address: mprcer@gmail.com.
authors.forename: Erica
authors.initials: E
authors.lastname: Rappold
authors.affiliation: Massachusetts General Hospital Biostatistics Center, Boston, MA, USA. Electronic address: dfinkelstein@partners.org.
authors.forename: Dianne M
authors.initials: DM
authors.lastname: Finkelstein
authors.affiliation: Massachusetts General Hospital, Boston, MA, USA. Electronic address: pgoss@partners.org.
authors.forename: Paul E
authors.initials: PE
authors.lastname: Goss
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics / Q000401:mortality / Q000473:pathology; D017024:Chemotherapy, Adjuvant; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D053208:Kaplan-Meier Estimate; D000077341:Lapatinib; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D009367:Neoplasm Staging; D018579:Patient Selection; D057285:Precision Medicine; D016016:Proportional Hazards Models; D047428:Protein Kinase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D011799:Quinazolines / Q000009:adverse effects / Q000627:therapeutic use*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D000077341:Lapatinib; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D018719:Erb-b2 Receptor Tyrosine Kinases; C508053:ERBB2 protein, human
keywords: Adjuvant; Early breast cancer; Hormone receptor; Lapatinib