Poziotinib treatment in patients with HER2-positive advanced breast cancer who have received prior anti-HER2 regimens.
Breast cancer
HER2
Metastatic
Poziotinib
Targeted therapy
Journal
Breast cancer research and treatment
ISSN: 1573-7217
Titre abrégé: Breast Cancer Res Treat
Pays: Netherlands
ID NLM: 8111104
Informations de publication
Date de publication:
23 Jan 2024
23 Jan 2024
Historique:
received:
19
05
2023
accepted:
22
11
2023
medline:
23
1
2024
pubmed:
23
1
2024
entrez:
23
1
2024
Statut:
aheadofprint
Résumé
Poziotinib is an irreversible pan-inhibitor of the human epidermal growth factor receptor (HER) that has shown acceptable tolerability and antitumor activity in phase I and II trials in patients with advanced solid tumors. In the present open-label, multicenter phase II study, we demonstrate safety, tolerability, and preliminary efficacy data from two different dosing schedules in patients with HER2-positive advanced breast cancer. Patients who had received at least two prior HER2-directed therapy lines for advanced disease, received 24 mg poziotinib on an intermittent dosing schedule (cohort 1) or 16 mg poziotinib once daily on a continuous dosing schedule (cohort 2). The primary endpoint was overall response rate (ORR). Secondary endpoints were progression-free survival (PFS), disease control rate (DCR), and time to progression (TTP). Secondary endpoints additionally included safety and pharmacokinetics. A total of 67 patients were enrolled. The ORR was 30% in both groups (p = 0.98). DCR was 60% vs 78% (p = 0.15) and median PFS and TTP were 4.1 vs 4.9 months (both p = 0.30) for cohorts 1 and 2, respectively. The most common treatment related adverse events (AEs) of any grade included diarrhea (88% vs 85%, p = 0.76), rash (88% vs 88%, p = 0.96), and stomatitis (64% vs 56%, p = 0.52), with grade 3-4 diarrhea occurring in 33% vs 32% of patients (p = 0.93) and grade 3-4 rash in 27% vs 35% of patients (p = 0.48) in cohort 1 vs cohort 2, respectively. Poziotinib demonstrated evidence of clinical activity in patients with pre-treated HER2-positive advanced breast cancer, although high levels of toxicity may preclude further studies at this time.
Identifiants
pubmed: 38261228
doi: 10.1007/s10549-023-07236-z
pii: 10.1007/s10549-023-07236-z
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.
Références
Howlader N, Altekruse SF, Li CI, Chen VW, Clarke CA, Ries LA et al (2014) US incidence of breast cancer subtypes defined by joint hormone receptor and HER2 status. J Natl Cancer Inst 106(5):dju055. https://doi.org/10.1093/jnci/dju055
doi: 10.1093/jnci/dju055
pubmed: 24777111
pmcid: 4580552
Loibl S, Gianni L (2017) HER2-positive breast cancer. Lancet 389(10087):2415–2429. https://doi.org/10.1016/S0140-6736(16)32417-5
doi: 10.1016/S0140-6736(16)32417-5
pubmed: 27939064
Smith AE, Ferraro E, Safonov A, Morales CB, Lahuerta EJA, Li Q et al (2021) HER2 + breast cancers evade anti-HER2 therapy via a switch in driver pathway. Nat Commun 12(1):6667. https://doi.org/10.1038/s41467-021-27093-y
doi: 10.1038/s41467-021-27093-y
pubmed: 34795269
pmcid: 8602441
Smyth LM, Piha-Paul SA, Won HH, Schram AM, Saura C, Loi S et al (2020) Efficacy and determinants of response to HER kinase inhibition in HER2-mutant metastatic breast cancer. Cancer Discov 10(2):198–213. https://doi.org/10.1158/2159-8290.CD-19-0966
doi: 10.1158/2159-8290.CD-19-0966
pubmed: 31806627
Razavi P, Chang MT, Xu G, Bandlamudi C, Ross DS, Vasan N et al (2018) The genomic landscape of endocrine-resistant advanced breast cancers. Cancer Cell. 34(3):427–38 e6. https://doi.org/10.1016/j.ccell.2018.08.008
doi: 10.1016/j.ccell.2018.08.008
pubmed: 30205045
pmcid: 6327853
Cocco E, Lopez S, Santin AD, Scaltriti M (2019) Prevalence and role of HER2 mutations in cancer. Pharmacol Ther 199:188–196. https://doi.org/10.1016/j.pharmthera.2019.03.010
doi: 10.1016/j.pharmthera.2019.03.010
pubmed: 30951733
pmcid: 6571037
Yi Z, Rong G, Guan Y, Li J, Chang L, Li H et al (2020) Molecular landscape and efficacy of HER2-targeted therapy in patients with HER2-mutated metastatic breast cancer. NPJ Breast Cancer 6:59. https://doi.org/10.1038/s41523-020-00201-9
doi: 10.1038/s41523-020-00201-9
pubmed: 33145402
pmcid: 7603305
Curigliano G, Mueller V, Borges V, Hamilton E, Hurvitz S, Loi S et al (2022) Tucatinib versus placebo added to trastuzumab and capecitabine for patients with pretreated HER2+ metastatic breast cancer with and without brain metastases (HER2CLIMB): final overall survival analysis. Ann Oncol 33(3):321–329. https://doi.org/10.1016/j.annonc.2021.12.005
doi: 10.1016/j.annonc.2021.12.005
pubmed: 34954044
Nasrazadani A, Brufsky A (2020) Neratinib: the emergence of a new player in the management of HER2+ breast cancer brain metastasis. Future Oncol 16(7):247–254. https://doi.org/10.2217/fon-2019-0719
doi: 10.2217/fon-2019-0719
pubmed: 32057254
Marti JLG, Hyder T, Nasrazadani A, Brufsky AM (2020) The evolving landscape of HER2-directed breast cancer therapy. Curr Treat Options Oncol 21(10):82. https://doi.org/10.1007/s11864-020-00780-6
doi: 10.1007/s11864-020-00780-6
pubmed: 32767149
Le X, Cornelissen R, Garassino M, Clarke JM, Tchekmedyian N, Goldman JW et al (2022) Poziotinib in non-small-cell lung cancer harboring HER2 Exon 20 insertion mutations after prior therapies: ZENITH20-2 trial. J Clin Oncol 40(7):710–718. https://doi.org/10.1200/JCO.21.01323
doi: 10.1200/JCO.21.01323
pubmed: 34843401
Tucker N. FDA denies approval of poziotinib for advanced/metastatic NSCLC with HER2 exon 20 insertions 2022. Available from: https://www.targetedonc.com/view/fda-denies-approval-of-poziotinib-for-advanced-metastatic-nsclc-with-her2-exon-20-insertions
Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R et al (2009) New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 45(2):228–47. https://doi.org/10.1016/j.ejca.2008.10.026
doi: 10.1016/j.ejca.2008.10.026
pubmed: 19097774
Kim TM, Lee KW, Oh DY, Lee JS, Im SA, Kim DW et al (2018) Phase 1 Studies of poziotinib, an irreversible Pan-HER tyrosine kinase inhibitor in patients with advanced solid tumors. Cancer Res Treat 50(3):835–842. https://doi.org/10.4143/crt.2017.303
doi: 10.4143/crt.2017.303
pubmed: 28859471
Park YH, Lee KH, Sohn JH, Lee KS, Jung KH, Kim JH et al (2018) A phase II trial of the pan-HER inhibitor poziotinib, in patients with HER2-positive metastatic breast cancer who had received at least two prior HER2-directed regimens: results of the NOV120101-203 trial. Int J Cancer 143(12):3240–3247. https://doi.org/10.1002/ijc.31651
doi: 10.1002/ijc.31651
pubmed: 29978467
von Minckwitz G, Huang CS, Mano MS, Loibl S, Mamounas EP, Untch M et al (2019) Trastuzumab emtansine for residual invasive HER2-positive breast cancer. N Engl J Med 380(7):617–628. https://doi.org/10.1056/NEJMoa1814017
doi: 10.1056/NEJMoa1814017
Cortes J, Kim SB, Chung WP, Im SA, Park YH, Hegg R et al (2022) Trastuzumab deruxtecan versus trastuzumab emtansine for breast cancer. N Engl J Med 386(12):1143–1154. https://doi.org/10.1056/NEJMoa2115022
doi: 10.1056/NEJMoa2115022
pubmed: 35320644
Kim HJ, Kim HP, Yoon YK, Kim MS, Lee GS, Han SW et al (2012) Antitumor activity of HM781-36B, a pan-HER tyrosine kinase inhibitor, in HER2-amplified breast cancer cells. Anticancer Drugs 23(3):288–297. https://doi.org/10.1097/CAD.0b013e32834e7d9b
doi: 10.1097/CAD.0b013e32834e7d9b
pubmed: 23422737
Robichaux JP, Elamin YY, Vijayan RSK, Nilsson MB, Hu L, He J et al (2019) Pan-cancer landscape and analysis of ERBB2 mutations identifies poziotinib as a clinically active inhibitor and enhancer of T-DM1 activity. Cancer Cell. 36(4):444–57 e7. https://doi.org/10.1016/j.ccell.2019.09.001
doi: 10.1016/j.ccell.2019.09.001
pubmed: 31588020
pmcid: 6944069
Kalra R, Chen CH, Wang J, Salam AB, Dobrolecki LE, Lewis A et al (2022) Poziotinib inhibits HER2-mutant-driven therapeutic resistance and multiorgan metastasis in breast cancer. Cancer Res 82(16):2928–2939. https://doi.org/10.1158/0008-5472.CAN-21-3106
doi: 10.1158/0008-5472.CAN-21-3106
pubmed: 35736563
pmcid: 9379360