@article{29439b8ae0e14af7b78d5e0b1140d8a2,
title = "HER kinase inhibition in patients with HER2-and HER3-mutant cancers",
abstract = "Somatic mutations of ERBB2 and ERBB3 (which encode HER2 and HER3, respectively) are found in a wide range of cancers. Preclinical modelling suggests that a subset of these mutations lead to constitutive HER2 activation, but most remain biologically uncharacterized. Here we define the biological and therapeutic importance of known oncogenic HER2 and HER3 mutations and variants of unknown biological importance by conducting a multi-histology, genomically selected, {\^a} €basket' trial using the pan-HER kinase inhibitor neratinib (SUMMIT; clinicaltrials.gov identifier NCT01953926). Efficacy in HER2-mutant cancers varied as a function of both tumour type and mutant allele to a degree not predicted by preclinical models, with the greatest activity seen in breast, cervical and biliary cancers and with tumours that contain kinase domain missense mutations. This study demonstrates how a molecularly driven clinical trial can be used to refine our biological understanding of both characterized and new genomic alterations with potential broad applicability for advancing the paradigm of genome-driven oncology.",
author = "Hyman, {David M.} and Piha-Paul, {Sarina A.} and Helen Won and Jordi Rodon and Cristina Saura and Shapiro, {Geoffrey I.} and Dejan Juric and Quinn, {David I.} and Victor Moreno and Bernard Doger and Mayer, {Ingrid A.} and Valentina Boni and Emiliano Calvo and Sherene Loi and Lockhart, {Albert C.} and Erinjeri, {Joseph P.} and Maurizio Scaltriti and Ulaner, {Gary A.} and Juber Patel and Jiabin Tang and Hannah Beer and {Duygu Selcuklu}, S. and Hanrahan, {Aphrothiti J.} and Nancy Bouvier and Myra Melcer and Rajmohan Murali and Schram, {Alison M.} and Smyth, {Lillian M.} and Komal Jhaveri and Li, {Bob T.} and Alexander Drilon and Harding, {James J.} and Gopa Iyer and Taylor, {Barry S.} and Berger, {Michael F.} and Cutler, {Richard E.} and Feng Xu and Anna Butturini and Eli, {Lisa D.} and Grace Mann and Cynthia Farrell and Lalani, {Alshad S.} and Bryce, {Richard P.} and Arteaga, {Carlos L.} and Funda Meric-Bernstam and Jos{\'e} Baselga and Solit, {David B.}",
note = "Funding Information: This work was funded by Puma Biotechnology, and supported by grants from the National Institutes of Health (grants P30 CA008748, P30 CA016672, P30 CA014089, R01 CA204749, R01 CA80195, T32 CA009207, 1U01 CA180964 and UL1 TR000371), the National Institutes of Health/National Cancer Institute (Breast SPORE grant P50 CA098131), Cycle for Survival, Marie-Jos{\'e}e and Henry R. Kravis Center for Molecular Oncology, The Cancer Prevention and Research Institute of Texas (RP1100584), the Sheikh Khalifa Bin Zayed Al Nahyan Institute for Personalized Cancer Therapy, Nellie B. Connally Breast Cancer Research Endowment, and the Breast Cancer Research Foundation. Funding Information: Acknowledgements We thank patients and their families for participating in this study. Editorial support, not including writing, was provided by L. Miller. This work was funded by Puma Biotechnology, and supported by grants from the National Institutes of Health (grants P30 CA008748, P30 CA016672, P30 CA014089, R01 CA204749, R01 CA80195, T32 CA009207, 1U01 CA180964 and UL1 TR000371), the National Institutes of Health/National Cancer Institute (Breast SPORE grant P50 CA098131), Cycle for Survival, Marie-Jos{\'e}e and Henry R. Kravis Center for Molecular Oncology, The Cancer Prevention and Research Institute of Texas (RP1100584), the Sheikh Khalifa Bin Zayed Al Nahyan Institute for Personalized Cancer Therapy, Nellie B. Connally Breast Cancer Research Endowment, and the Breast Cancer Research Foundation. Publisher Copyright: {\textcopyright} 2018 Macmillan Publishers Limited, part of Springer Nature. All rights reserved.",
year = "2018",
month = feb,
day = "8",
doi = "10.1038/nature25475",
language = "English (US)",
volume = "554",
pages = "189--194",
journal = "Nature",
issn = "0028-0836",
publisher = "Nature Publishing Group",
number = "7691",
}