FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W3134169755> ?p ?o ?g. }

• W3134169755 endingPage "100063" @default.
• W3134169755 startingPage "100063" @default.
• W3134169755 abstract "On 10 December 2020, the European Medicines Agency's (EMA) Committee for Medicinal Products for Human Use (CHMP) adopted a positive opinion, recommending the granting of a marketing authorization for Tukysa (tucatinib) in combination with trastuzumab and capecitabine for the treatment of adult patients with human epidermal growth factor receptor 2 (HER2)-positive locally advanced or metastatic breast cancer (BC) who have received at least two prior anti-HER2 treatment regimens.1EMA: summary of CHMP positive opinion about Tukysa (tucatinib).https://bit.ly/37TlI34Google Scholar The EMA's recommendation is mainly based on the HER2CLIMB phase II trial, which randomized BC patients to receive trastuzumab and capecitabine with either tucatinib or placebo. Tucatinib demonstrated efficacy compared with placebo in terms of both progression-free survival (PFS) and overall survival (OS).2Murthy R.K. Loi S. Okines A. et al.Tucatinib, trastuzumab, and capecitabine for HER2-positive metastatic breast cancer.N Engl J Med. 2020; 382: 597-609Crossref PubMed Scopus (256) Google Scholar A key unique feature of the HER2CLIMB trial was that, out of the ∼600 patients enrolled, 291 patients had brain metastases (BMs) at baseline. Furthermore, of these 291 patients, 60% had new or active BMs at study entry, defined as either new lesions or untreated lesions at baseline, or previously treated but progressing existing lesions. Of note, such patients have been traditionally excluded from enrollment in clinical trials. This is the first randomized trial in which an OS benefit for patients with BC and BMs was observed, which is an unmet medical need, especially in HER2-positive metastatic BC, where the occurrence of BMs is frequent, with at least half of patients developing BMs over the course of their disease. Until now, we had no drugs approved for the systemic treatment of BMs. In light of these clinical results, EMA's announcement about tucatinib expands options for HER2-positive advanced BC (ABC). Approximately 15%-20% of BCs overexpress HER2.3Owens M.A. Horten B.C. Da Silva M.M. HER2 amplification ratios by fluorescence in situ hybridization and correlation with immunohistochemistry in a cohort of 6556 breast cancer tissues.Clin Breast Cancer. 2004; 5: 63-69Abstract Full Text PDF PubMed Scopus (514) Google Scholar To date, the standard of care in first-line treatment of patients with HER2-positive ABC is trastuzumab plus pertuzumab and a taxane. In second-line treatment, trastuzumab emtansine (T-DM1) is the treatment of choice. For patients with HER2-positive BC progressing during or within 12 months after adjuvant trastuzumab, T-DM1 is considered the standard first-line treatment. Although systemic treatment options have improved over the past two decades, most patients with HER2-positive metastatic BC eventually die of their disease.4Suh J.H. Kotecha R. Chao S.T. Ahluwalia M.S. Sahgal A. Chang El Current approaches to the management of brain metastases.Nat Rev Clin Oncol. 2020; 17: 279-299Crossref PubMed Scopus (50) Google Scholar In addition, as newly discovered regimens prolong survival, the incidence of BMs, for which active treatment options are limited, increases.5Swain S.M. Kim S.B. Cortés J. et al.Pertuzumab, trastuzumab, and docetaxel for HER2-positive metastatic breast cancer (CLEOPATRA study): overall survival results from a randomised, double-blind, placebo-controlled, phase 3 study.Lancet Oncol. 2013; 14: 461-471Abstract Full Text Full Text PDF PubMed Scopus (666) Google Scholar,6Bendell J.C. Domchek S.M. Burstein H.J. et al.Central nervous system metastases in women who receive trastuzumab-based therapy for metastatic breast carcinoma.Cancer. 2003; 97: 2972-2977Crossref PubMed Scopus (586) Google Scholar Treatment of BMs includes locoregional approaches, such as neurosurgical resection and stereotactic or whole-brain radiation therapy.7Pestalozzi B.C. Holmes E. De Azambuja E. et al.CNS relapses in patients with HER2-positive early breast cancer who have and have not received adjuvant trastuzumab: a retrospective substudy of the HERA trial (BIG 1-01).Lancet Oncol. 2013; 14: 244-248Abstract Full Text Full Text PDF PubMed Scopus (113) Google Scholar However, systemic drugs, including HER2-targeted agents and chemotherapy, exert a limited intracranial antitumor activity. Such an issue is even more complicated due to the under-representation of patients with BMs in randomized, clinical trials, which usually exclude such patients, thus lacking solid data.8Lin N.U. Diéras V. Paul D. et al.Multicenter phase II study of lapatinib in patients with brain metastases from HER2-positive breast cancer.Clin Cancer Res. 2009; 15: 1452-1459Crossref PubMed Scopus (485) Google Scholar, 9Krop I.E. Lin N.U. Blackwell K. et al.Trastuzumab emtansine (T-DM1) versus lapatinib plus capecitabine in patients with HER2-positive metastatic breast cancer and central nervous system metastases: a retrospective, exploratory analysis in EMILIA.Ann Oncol. 2015; 26: 113-119Abstract Full Text Full Text PDF PubMed Scopus (200) Google Scholar, 10Freedman R.A. Gelman R.S. Anders C.K. et al.TBCRC 022: a phase II trial of neratinib and capecitabine for patients with human epidermal growth factor receptor 2-positive breast cancer and brain metastases.J Clin Oncol. 2019; 37: 1081-1089Crossref PubMed Scopus (117) Google Scholar Tucatinib is an oral tyrosine kinase inhibitor (TKI) highly selective for the kinase domain of HER2, with minimal inhibition of epidermal growth factor receptor.11Moulder S.L. Borges V.F. Baetz T. et al.Phase I study of ONT-380, a HER2 inhibitor, in patients with HER2.Clin Cancer Res. 2017; 23: 3529-3536Crossref PubMed Scopus (68) Google Scholar During its preclinical characterization and in the early-phase clinical settings, tucatinib has demonstrated efficient brain penetration.12Kulukian A. Lee P. Taylor J. et al.Preclinical activity of HER2-selective tyrosine kinase inhibitor tucatinib as a single agent or in combination with trastuzumab or docetaxel in solid tumor models.Mol Cancer Ther. 2020; 19: 976-987Crossref PubMed Scopus (29) Google Scholar,13Lee A.J. Jiang J. Kumar V. Alley S.C. Peterson S. Li J. 295P: physiologically based pharmacokinetic (PBPK) modeling of the central nervous system (CNS) pharmacokinetics of tucatinib in patients with breast cancer brain metastasis.Ann Oncol. 2020; 31: S360Abstract Full Text Full Text PDF Google Scholar In a phase 1b dose escalation trial started in 2008, the combination of tucatinib with trastuzumab and capecitabine displayed promising antitumor activity in patients with HER2-positive metastatic BC, including those with BMs (Table 1).11Moulder S.L. Borges V.F. Baetz T. et al.Phase I study of ONT-380, a HER2 inhibitor, in patients with HER2.Clin Cancer Res. 2017; 23: 3529-3536Crossref PubMed Scopus (68) Google Scholar The approval was based on the results of the phase II HER2CLIMB trial, which randomized HER2-positive BC patients to receive trastuzumab and capecitabine with either tucatinib or placebo.2Murthy R.K. Loi S. Okines A. et al.Tucatinib, trastuzumab, and capecitabine for HER2-positive metastatic breast cancer.N Engl J Med. 2020; 382: 597-609Crossref PubMed Scopus (256) Google Scholar Tucatinib demonstrated efficacy compared with placebo in PFS [7.8 months versus 5.6 months; hazard ratio (HR): 0.54, 95% confidence interval (CI): 0.42-0.71, P < 0.001] and OS (21.9 months versus 17.4 months; HR: 0.66, 95% CI: 0.50-0.87, P = 0.0048).2Murthy R.K. Loi S. Okines A. et al.Tucatinib, trastuzumab, and capecitabine for HER2-positive metastatic breast cancer.N Engl J Med. 2020; 382: 597-609Crossref PubMed Scopus (256) Google Scholar Prior treatment with capecitabine or lapatinib were exclusion criteria, although patients who had received lapatinib >12 months before enrollment were eligible.2Murthy R.K. Loi S. Okines A. et al.Tucatinib, trastuzumab, and capecitabine for HER2-positive metastatic breast cancer.N Engl J Med. 2020; 382: 597-609Crossref PubMed Scopus (256) Google Scholar Among the 511 patients with measurable disease at baseline, an objective response was confirmed in 40.6% (95% CI: 35.3-46.0) of patients in the tucatinib-combination group and 22.8% (95% CI: 16.7-29.8) of patients in the placebo-combination group (P < 0.001).2Murthy R.K. Loi S. Okines A. et al.Tucatinib, trastuzumab, and capecitabine for HER2-positive metastatic breast cancer.N Engl J Med. 2020; 382: 597-609Crossref PubMed Scopus (256) Google Scholar Notably, patients with untreated BMs were allowed to enter the study, unless immediate management was needed, in which case they could be enrolled after local intervention.2Murthy R.K. Loi S. Okines A. et al.Tucatinib, trastuzumab, and capecitabine for HER2-positive metastatic breast cancer.N Engl J Med. 2020; 382: 597-609Crossref PubMed Scopus (256) Google Scholar Overall, patients with BMs represented 48% (N = 198, tucatinib arm) and 46% (N = 93, control arm) of the study population, with median duration of PFS of 7.6 months (95% CI: 6.2-9.5) and 5.4 months (95% CI: 4.1-5.7) for the experimental and control arm, respectively. An exploratory subgroup analysis specifically focused on patients harboring BMs (N = 291) disclosed that the addition of tucatinib improved intracranial PFS (9.9 months versus 4.2 months, P < 0.0001; HR: 0.48, 95% CI: 0.34-0.69, P < 0.00001) and OS (18.1 months versus 12 months, P = 0.005; OS HR, 0.58; 95% CI: 0.40-0.85; P = 0.005).14Lin N.U. Borges V. Anders C. et al.Intracranial efficacy and survival with tucatinib plus trastuzumab and capecitabine for previously treated HER2-positive breast cancer with brain metastases in the HER2CLIMB trial.J Clin Oncol. 2020; 38: 2610-2619Crossref PubMed Scopus (74) Google Scholar Finally, among the 75 patients with active BMs and measurable intracranial disease at baseline, intracranial objective response rate was improved (47.3% versus 20%, P = 0.03).14Lin N.U. Borges V. Anders C. et al.Intracranial efficacy and survival with tucatinib plus trastuzumab and capecitabine for previously treated HER2-positive breast cancer with brain metastases in the HER2CLIMB trial.J Clin Oncol. 2020; 38: 2610-2619Crossref PubMed Scopus (74) Google Scholar Such results are consistent with the efficient brain penetration of tucatinib (Table 2).11Moulder S.L. Borges V.F. Baetz T. et al.Phase I study of ONT-380, a HER2 inhibitor, in patients with HER2.Clin Cancer Res. 2017; 23: 3529-3536Crossref PubMed Scopus (68) Google Scholar,12Kulukian A. Lee P. Taylor J. et al.Preclinical activity of HER2-selective tyrosine kinase inhibitor tucatinib as a single agent or in combination with trastuzumab or docetaxel in solid tumor models.Mol Cancer Ther. 2020; 19: 976-987Crossref PubMed Scopus (29) Google Scholar The most common adverse events in the tucatinib arm were diarrhea (any grade: 80% versus 53% in the control arm; grade ≥ 3 diarrhea: 12.9% versus 8.6% in the control arm), palmar-plantar erythrodysesthesia syndrome, fatigue, nausea, and vomiting (Table 2).2Murthy R.K. Loi S. Okines A. et al.Tucatinib, trastuzumab, and capecitabine for HER2-positive metastatic breast cancer.N Engl J Med. 2020; 382: 597-609Crossref PubMed Scopus (256) Google Scholar Patients in the tucatinib arm experienced a higher rate of transaminitis, even though typically low-grade, transient, and reversible.2Murthy R.K. Loi S. Okines A. et al.Tucatinib, trastuzumab, and capecitabine for HER2-positive metastatic breast cancer.N Engl J Med. 2020; 382: 597-609Crossref PubMed Scopus (256) Google Scholar So, the recent recommendation of the CHMP for marketing authorization in the European Union (EU) is only the most recent achievement in the history of a compound that in 2016 was granted Fast Track designation in the USA, in 2017 gained Orphan Drug designation for BMs, and in 2019 Breakthrough Therapy Designation by the Food and Drug Administration (FDA). Tucatinib is already marketed in the USA, where on 17 April 2020, the FDA issued approval to this drug in combination with trastuzumab and capecitabine for adult patients with advanced unresectable or metastatic HER2-positive BC, including those with BMs, who have received one or more prior anti-HER2-based regimens in the metastatic setting.15FDA approves tucatinib for patients with HER2-positive metastatic breast cancer.https://bit.ly/3mOnvKYDate: 2020Google Scholar In the European World Health Organization (WHO) region, tucatinib has been approved only in Switzerland, where on 12 May 2020 the Swiss Agency for Therapeutic Products (Swissmedic) granted approval to the drug with the same indications provided by the FDA.16Seattle Genetics Announces the Approval of TUKYSA™ (tucatinib) in Switzerland for the Treatment of Patients with Metastatic HER2-Positive Breast Cancer.https://bit.ly/38FLXZEDate: 2020Google Scholar The approvals stand for the first time under the aegis of Project Orbis, an initiative of the FDA Oncology Center of Excellence that provides a framework for concurrent submission and review of oncology products among international partners.15FDA approves tucatinib for patients with HER2-positive metastatic breast cancer.https://bit.ly/3mOnvKYDate: 2020Google Scholar,16Seattle Genetics Announces the Approval of TUKYSA™ (tucatinib) in Switzerland for the Treatment of Patients with Metastatic HER2-Positive Breast Cancer.https://bit.ly/38FLXZEDate: 2020Google Scholar Among them, the Australian Therapeutic Goods Administration granted approval on 12 August 2020, after Canada and Singapore. In the EU, the Marketing Authorization Application for tucatinib was validated by EMA in January 2020. On 10 December 2020, the CHMP adopted a positive opinion, recommending the granting of the marketing authorization.1EMA: summary of CHMP positive opinion about Tukysa (tucatinib).https://bit.ly/37TlI34Google Scholar The successful story of the HER2 gene, identified in 1982-1984, evolved with the identification of HER2-positive BC and the quest for targeted agents.16Seattle Genetics Announces the Approval of TUKYSA™ (tucatinib) in Switzerland for the Treatment of Patients with Metastatic HER2-Positive Breast Cancer.https://bit.ly/38FLXZEDate: 2020Google Scholar, 17Lee A. Tucatinib: first approval.Drugs. 2020; 80: 1033-1038Crossref PubMed Scopus (12) Google Scholar, 18Tarantino P. Prat A. Cortes J. Cardoso F. Curigliano G. Third-line treatment of HER2-positive advanced breast cancer: from no standard to a Pandora's box.Biochim Biophys Acta Rev Cancer. 2020; 1875: 188487Crossref PubMed Scopus (5) Google Scholar Years later, tucatinib was developed by Array BioPharma and licensed to Cascadian Therapeutics (subsequently part of Seattle Genetics).17Lee A. Tucatinib: first approval.Drugs. 2020; 80: 1033-1038Crossref PubMed Scopus (12) Google Scholar Ultimately, the forthcoming EMA's registration of tucatinib for HER2-positive ABC represents another achievement in a scientific saga lasting for more than three decades (Figure 1). This further step will represent for many European patients the availability of a new valuable therapeutic option. Indeed, the third-line treatment of HER2-positive ABC has traditionally been considered a field of uncertainty, since decisions were taken upon studies enrolling a patient population different from the one treated to date.18Tarantino P. Prat A. Cortes J. Cardoso F. Curigliano G. Third-line treatment of HER2-positive advanced breast cancer: from no standard to a Pandora's box.Biochim Biophys Acta Rev Cancer. 2020; 1875: 188487Crossref PubMed Scopus (5) Google Scholar Although the lack of comparative studies did not allow for recommendations about any specific sequencing, the development of novel anti-HER2 agents rapidly affected the field and shaped recent guidelines.19Cardoso F. Paluch-Shimon S. Senkus E. et al.5th ESO-ESMO international consensus guidelines for advanced breast cancer (ABC 5).Ann Oncol. 2020; 31: 1623-1649Abstract Full Text Full Text PDF PubMed Scopus (122) Google Scholar In this regard, the recently FDA-approved tucatinib-based combination represents a further valid choice, with the added value of its intracranial and extracranial efficacy in patients with BMs.2Murthy R.K. Loi S. Okines A. et al.Tucatinib, trastuzumab, and capecitabine for HER2-positive metastatic breast cancer.N Engl J Med. 2020; 382: 597-609Crossref PubMed Scopus (256) Google Scholar With the evolving therapeutic options in the landscape of HER2-positive ABC, improving patient selection is more and more crucial. In the near future, we will be called to optimally manage and sequence all the available drugs, considering also that some patients will have received T-DM1 in the adjuvant setting, in case of residual invasive disease after completion of neoadjuvant therapy, and the new drugs that are enriching the therapeutic armamentarium, such as the earlier discussed tucatinib as well as trastuzumab-deruxtecan.20Von Minckwitz G. Huang C.S. Mano M.S. et al.Trastuzumab emtansine for residual invasive HER2-positive breast cancer.N Engl J Med. 2019; 380: 617-628Crossref PubMed Scopus (610) Google Scholar,21Modi S. Saura C. Yamashita T. et al.Trastuzumab deruxtecan in previously treated HER2-positive breast cancer.N Engl J Med. 2020; 382: 610-621Crossref PubMed Scopus (310) Google Scholar In an ideal world, rapid access to all newly available anticancer drugs should be guaranteed to all patients. However, this is far from the reality, as access to new cancer medicines differs significantly across different countries.22Wilking N. Bucsics A. Kandolf Sekulovic L. et al.Achieving equal and timely access to innovative anticancer drugs in the European Union (EU): summary of a multidisciplinary CECOG-driven roundtable discussion with a focus on Eastern and South-Eastern EU countries.ESMO Open. 2019; 4: e000550Abstract Full Text Full Text PDF PubMed Scopus (7) Google Scholar The two key aspects for those involved in reimbursement decisions are the level of evidence required to decide and pricing, which can be challenging for some innovative oncology compounds such as tucatinib.22Wilking N. Bucsics A. Kandolf Sekulovic L. et al.Achieving equal and timely access to innovative anticancer drugs in the European Union (EU): summary of a multidisciplinary CECOG-driven roundtable discussion with a focus on Eastern and South-Eastern EU countries.ESMO Open. 2019; 4: e000550Abstract Full Text Full Text PDF PubMed Scopus (7) Google Scholar Since ESMO has declared achieving equal access to cancer care as one of its major goals, we hope that cooperation and dialogue between stakeholders will ensure that high-quality cost-effective medical oncology care will include compounds such as the newcomer tucatinib .Table 1Key clinical trials of tucatinib for breast cancer patientsIDDrug(s)IndicationPhaseStatusHER2CLIMB-02NCT03975647Tucatinib, T-DM1HER2-positive metastatic BCIIIRecruitingI-SPY 2NCT01042379Tucatinib, chemotherapyBCIIRecruitingNCT03501979Tucatinib, capecitabine, trastuzumabLeptomeningeal metastases in HER2-positive metastatic BCIIRecruitingHER2CLIMB-04NCT04539938Tucatinib with T-DXdHER2-positive metastatic BCIIRecruitingHER2CLIMBNCT02614794Tucatinib, placebo, capecitabine, trastuzumabHER2-positive metastatic BCIIActive, not recruitingTRIPLET NCT02025192Tucatinib, capecitabine, trastuzumabHER2-positive metastatic BCIbCompletedNCT01983501Tucatinib, T-DM1HER2-positive metastatic BCIbCompletedNCT00650572TucatinibHER2-positive solid malignanciesICompletedBC, breast cancer; HER2, human epidermal growth factor receptor 2; ID, identifier; T-DM1, trastuzumab emtansine; T-DXd, trastuzumab deruxtecan. Open table in a new tab Table 2Features and properties of tucatinibChemical nameN6-(4,4-dimethyl-4,5-dihydrooxazol-2-yl)-N4-[3-methyl-4-([1,2,4] triazolo[1,5-a]pyridin-7-yloxy)phenyl]quinazoline-4,6-diamineAlternative namesONT-380, ARRY-380, irbinitinib, 937263-43-9, Tukysa (tradename)ClassSmall molecule, TKIMoAHighly selective for the kinase domain of HER2, minimal inhibition of EGFR. Prevention of signal transduction pathways, resulting in growth inhibition and cell death.RouteOral administrationPDHER2 IC50 6.9 nmol/lPKVd ≈ 1670 l, plasma protein binding 97%, CL 148 l/h, half-life ≈ 8.5 hCNS penetrationaInformation about CNS penetration is based on a whole-body physiologically-based pharmacokinetic (PBPK) model integrated with a four-compartment permeability-limited brain model developed and verified for predicting tucatinib concentration-time profiles in the plasma, cerebrospinal fluid, brain, and brain tumors.: high passive permeability (Papp, 12.6 × 10−6 cm/s).Normal brain: Css,ave = 5.37 ng/ml (TER, 1.6), (Kp,uu) 0.47.Brain tumors: Css,ave 15.6 ng/ml (TER, 4.7), Kp,uu = 1.37 (↑ drug penetration).AEsCommon: diarrhea, palmar-plantar erythrodysesthesia syndrome, anemia, decreased phosphate, nausea.Sporadic: hepatotoxicity (↑ALT, ↑AST, ↑ALP, ↑bilirubin), vomiting, stomatitis, decreased appetite, rash, renal impairment (increased creatinine, decreased magnesium, potassium, or sodium).Infrequent: arthralgia, weight decreases, peripheral neuropathy, epistaxis.AEs, adverse events; ALP, alkaline phosphatase2Murthy R.K. Loi S. Okines A. et al.Tucatinib, trastuzumab, and capecitabine for HER2-positive metastatic breast cancer.N Engl J Med. 2020; 382: 597-609Crossref PubMed Scopus (256) Google Scholar,13Lee A.J. Jiang J. Kumar V. Alley S.C. Peterson S. Li J. 295P: physiologically based pharmacokinetic (PBPK) modeling of the central nervous system (CNS) pharmacokinetics of tucatinib in patients with breast cancer brain metastasis.Ann Oncol. 2020; 31: S360Abstract Full Text Full Text PDF Google Scholar; ALT, alanine aminotransferase; AST, aspartate aminotransferase; CL, clearance; CNS, central nervous system; Css,ave, steady-state average concentration; EGFR, epidermal growth factor receptor; HER2, human epidermal growth factor receptor 2; IC50, half maximal inhibitory concentration; Kp,uu, unbound brain-to-unbound plasma concentration ratio; MoA, mechanism of action; N, nitrogen; Papp, passive permeability; PD, pharmacodynamics; PK, pharmacokinetics; TER, target engagement ratio; TKI, tyrosine kinase inhibitor; Vd, volume of distribution; ↑, increased.a Information about CNS penetration is based on a whole-body physiologically-based pharmacokinetic (PBPK) model integrated with a four-compartment permeability-limited brain model developed and verified for predicting tucatinib concentration-time profiles in the plasma, cerebrospinal fluid, brain, and brain tumors. Open table in a new tab BC, breast cancer; HER2, human epidermal growth factor receptor 2; ID, identifier; T-DM1, trastuzumab emtansine; T-DXd, trastuzumab deruxtecan. AEs, adverse events; ALP, alkaline phosphatase2Murthy R.K. Loi S. Okines A. et al.Tucatinib, trastuzumab, and capecitabine for HER2-positive metastatic breast cancer.N Engl J Med. 2020; 382: 597-609Crossref PubMed Scopus (256) Google Scholar,13Lee A.J. Jiang J. Kumar V. Alley S.C. Peterson S. Li J. 295P: physiologically based pharmacokinetic (PBPK) modeling of the central nervous system (CNS) pharmacokinetics of tucatinib in patients with breast cancer brain metastasis.Ann Oncol. 2020; 31: S360Abstract Full Text Full Text PDF Google Scholar; ALT, alanine aminotransferase; AST, aspartate aminotransferase; CL, clearance; CNS, central nervous system; Css,ave, steady-state average concentration; EGFR, epidermal growth factor receptor; HER2, human epidermal growth factor receptor 2; IC50, half maximal inhibitory concentration; Kp,uu, unbound brain-to-unbound plasma concentration ratio; MoA, mechanism of action; N, nitrogen; Papp, passive permeability; PD, pharmacodynamics; PK, pharmacokinetics; TER, target engagement ratio; TKI, tyrosine kinase inhibitor; Vd, volume of distribution; ↑, increased. None declared." @default.
• W3134169755 created "2021-03-15" @default.
• W3134169755 creator A5000459628 @default.
• W3134169755 creator A5022239860 @default.
• W3134169755 date "2021-04-01" @default.
• W3134169755 modified "2023-10-11" @default.
• W3134169755 title "Tucatinib approval by EMA expands options for HER2-positive locally advanced or metastatic breast cancer" @default.
• W3134169755 cites W2000798782 @default.
• W3134169755 cites W2013669698 @default.
• W3134169755 cites W2120661754 @default.
• W3134169755 cites W2125401809 @default.
• W3134169755 cites W2129749518 @default.
• W3134169755 cites W2168814163 @default.
• W3134169755 cites W2571057012 @default.
• W3134169755 cites W2902218997 @default.
• W3134169755 cites W2921590809 @default.
• W3134169755 cites W2984738731 @default.
• W3134169755 cites W2995808512 @default.
• W3134169755 cites W2996630100 @default.
• W3134169755 cites W3007679475 @default.
• W3134169755 cites W3015126839 @default.
• W3134169755 cites W3030461309 @default.
• W3134169755 cites W3034949147 @default.
• W3134169755 cites W3089012529 @default.
• W3134169755 cites W3108021649 @default.
• W3134169755 cites W4206666777 @default.
• W3134169755 doi "https://doi.org/10.1016/j.esmoop.2021.100063" @default.
• W3134169755 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/8103530" @default.
• W3134169755 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/33676293" @default.
• W3134169755 hasPublicationYear "2021" @default.
• W3134169755 type Work @default.
• W3134169755 sameAs 3134169755 @default.
• W3134169755 citedByCount "7" @default.
• W3134169755 countsByYear W31341697552021 @default.
• W3134169755 countsByYear W31341697552022 @default.
• W3134169755 countsByYear W31341697552023 @default.
• W3134169755 crossrefType "journal-article" @default.
• W3134169755 hasAuthorship W3134169755A5000459628 @default.
• W3134169755 hasAuthorship W3134169755A5022239860 @default.
• W3134169755 hasBestOaLocation W31341697551 @default.
• W3134169755 hasConcept C121608353 @default.
• W3134169755 hasConcept C126322002 @default.
• W3134169755 hasConcept C143998085 @default.
• W3134169755 hasConcept C2775930923 @default.
• W3134169755 hasConcept C530470458 @default.
• W3134169755 hasConcept C71924100 @default.
• W3134169755 hasConceptScore W3134169755C121608353 @default.
• W3134169755 hasConceptScore W3134169755C126322002 @default.
• W3134169755 hasConceptScore W3134169755C143998085 @default.
• W3134169755 hasConceptScore W3134169755C2775930923 @default.
• W3134169755 hasConceptScore W3134169755C530470458 @default.
• W3134169755 hasConceptScore W3134169755C71924100 @default.
• W3134169755 hasIssue "2" @default.
• W3134169755 hasLocation W31341697551 @default.
• W3134169755 hasLocation W31341697552 @default.
• W3134169755 hasLocation W31341697553 @default.
• W3134169755 hasOpenAccess W3134169755 @default.
• W3134169755 hasPrimaryLocation W31341697551 @default.
• W3134169755 hasRelatedWork W1999702412 @default.
• W3134169755 hasRelatedWork W2001196910 @default.
• W3134169755 hasRelatedWork W2037317309 @default.
• W3134169755 hasRelatedWork W2077649377 @default.
• W3134169755 hasRelatedWork W2165595478 @default.
• W3134169755 hasRelatedWork W2557359331 @default.
• W3134169755 hasRelatedWork W2892677547 @default.
• W3134169755 hasRelatedWork W2955569507 @default.
• W3134169755 hasRelatedWork W3200352014 @default.
• W3134169755 hasRelatedWork W3203106735 @default.
• W3134169755 hasVolume "6" @default.
• W3134169755 isParatext "false" @default.
• W3134169755 isRetracted "false" @default.
• W3134169755 magId "3134169755" @default.
• W3134169755 workType "article" @default.