New anti-HER2 agents for brain metastasis: histology-agnostic weapons?
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LETTER TO THE EDITOR
New anti‑HER2 agents for brain metastasis: histology‑agnostic weapons? Paolo Tarantino1,2 · Aleix Prat3,4 · Giuseppe Curigliano1,2 Received: 6 October 2020 / Accepted: 13 October 2020 © Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Besides predicting responsiveness to anti-HER2 agents, HER2 aberrations are associated with a high incidence of central nervous system (CNS) metastasis across several cancer types, including breast, lung, gastric and colorectal cancer. In this setting, several novel anti-HER2 agents with relevant CNS activity are emerging, including tucatinib and trastuzumab deruxtecan. Both agents are already FDA-approved for treating advanced breast cancer, but are also being tested for the treatment of other HER2-driven histologies. The confirmation of their activity in other cancer types may provide histology-agnostic weapons against HER2-driven brain metastasis, possibly improving the prognosis of a wide population of cancer patients. Keywords HER2 · Brain metastasis · Histology-agnostic · Tucatinib · Antibody–drug conjugates · Trastuzumab deruxtecan The recognition of the oncogenic role of HER2 has led to some of the most remarkable advancements in the treatment of cancer. Multiple agents targeting HER2 are today approved to treat both early and advanced breast cancer (BC), with a relevant impact on patient’s survival. Following the “BC experience”, the anti-HER2 agent trastuzumab was experimented in advanced HER2-positive gastric cancer, and subsequently approved as first-line treatment in combination with chemotherapy. However, HER2 aberrations are found ubiquitously in oncology and, in the last decade, the lessons learnt in breast and gastric cancer were translated to other cancer histologies. Indeed, about 2% of non-small-cell lung cancers (NSCLC) harbor HER2 oncogenic mutations, [1] and 5% of RAS-wild type metastatic colorectal cancers show HER2-amplifications [2]. Importantly, in both of these settings HER2-blockade with different compounds has shown early encouraging results [3, 4]. Besides predicting response to targeted agents, HER2 aberrations are associated with distinct features of tumor * Giuseppe Curigliano [email protected] 1
European Institute of Oncology IRCCS, Milan, Italy
2
University of Milan, Milan, Italy
3
Translational Genomics and Targeted Therapies in Solid Tumors, IDIBAPS, Barcelona, Spain
4
University of Barcelona, Barcelona, Spain
behavior. In particular, it is widely recognized that HER2positive BC patients present a much higher incidence of central nervous system (CNS) metastasis compared with HER2-negative patients, with about one-fourth of metastatic patients developing CNS disease during the course of the disease [5]. This may be due to both the biology of this oncogene-driven disease and/or the sanctuary nature of the CNS, which hinders the activity of anti-HER2 treatments. Notably, in the past few years, several reports have suggested that other HER2-driven cancer-types may share the
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