Targeted therapy in HER2-positive breast cancer

Li, Shu Guang; Li, Li

doi:10.3892/br.2013.95

Cited by 45 publications

(30 citation statements)

References 72 publications

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“…Among all patients treated with sunitinib, the median PFS was 11.6 m (95% CI: [6][7][8][9][10][11][12][13][14][15][16][17][18][19]. Median PFS was 21 m (95% CI: 11-25) for macrocytic patients compared to 4 m (95% CI: 3-8) in normocytic patients (P = 0.0001) (Fig.…”

Section: Resultsmentioning

confidence: 99%

Clinical significance of sunitinib‐associated macrocytosis in metastatic renal cell carcinoma

et al. 2016

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Increases in the mean corpuscular volume (MCV) have been observed in patients with metastatic renal cell carcinoma (mRCC) on tyrosine kinase inhibitor (TKI) treatment; however, its association with progression‐free‐survival (PFS) is unknown. We aimed to characterize TKI‐associated macrocytosis in mRCC and its relationship with PFS. Retrospective review of data on macrocytosis and thyroid dysfunction on mRCC patients treated with sunitinib and/or sorafenib. These results are evaluated in the context of our previous report on the association of hypothyroidism in this setting. We assessed PFS as clinically defined by the treating physician. Seventy‐four patients, 29 of whom received both drugs, were included. A treatment period was defined as time from initiation to discontinuation of either sunitinib or sorafenib; 103 treatment periods [sorafenib (47), sunitinib (56)] were analyzed. Macrocytosis was found in 55 and 8% of sunitinib‐ and sorafenib‐treated patients, respectively, P < 0.001. The median time to developing macrocytosis was 3 months (m, range 1–7). Median PFS in sunitinib‐treated patients was 11 m (95% CI: 6–19). Median PFS was higher among those with macrocytosis compared to normocytosis (21 m [95% CI: 11–25] vs. 4 m [95% CI: 3–8] P = 0.0001). Macrocytosis and hypothyroidism were two significant predictors of PFS. The greatest difference in PFS among all patients was observed in patients with both macrocytosis and hypothyroidism (25 m), compared to the normocytic and euthyroid patients (5 m) (P < 0.0001). Sunitinib‐related macrocytosis was associated with prolonged PFS, and concurrent development of hypothyroidism and macrocytosis further prolonged PFS. Increased MCV may have a role as a predictive biomarker for sunitinib. Prospective studies accounting for other known prognostic factors are needed to confirm this finding.

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Section: Resultsmentioning

confidence: 99%

Clinical significance of sunitinib‐associated macrocytosis in metastatic renal cell carcinoma

et al. 2016

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“…However, in terms of a therapeutic approach, the use of trastuzumab, a specific chemotherapeutic agent targeting HER2, dramatically improves disease-free survival and overall survival in HER2-positive patients with breast carcinoma (Li and Li 2013). Because there is no consensus with regard to the selection criteria for HER2-targeted therapy in eyelid SbGC, the ASCO/CAP guidelines for breast cancer may represent an alternate or a reference (Wolff et al 2013).…”

Section: Discussionmentioning

confidence: 99%

Increased gene copy number of HER2 and concordant protein overexpression found in a subset of eyelid sebaceous gland carcinoma indicate HER2 as a potential therapeutic target

Lee

Kim

Choung

et al. 2015

J Cancer Res Clin Oncol

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“…Although multiple approved strategies exist for disrupting HER2 signaling in HER2-positive (HER2 þ ) metastatic breast cancer (MBC; refs. 4,5), including mAbs such as trastuzumab (6) and pertuzumab (7), the antibody-drug conjugate ado-trastuzumab emtansine (T-DM1; ref. 8), and the small-molecule dual tyrosine kinase inhibitor (TKI) lapatinib (9), several unmet needs exist in this patient population.…”

Section: Introductionmentioning

confidence: 99%

Phase I Study of ONT-380, a HER2 Inhibitor, in Patients with HER2+-Advanced Solid Tumors, with an Expansion Cohort in HER2+ Metastatic Breast Cancer (MBC)

Moulder

Borges

Baetz

et al. 2017

Clinical Cancer Research

116

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ONT-380 (ARRY-380) is a potent and selective oral HER2 inhibitor. This Phase I study determined the MTD, pharmacokinetics (PK) and antitumor activity of ONT-380 in HER2-positive advanced solid tumors, with an expansion cohort of patients with HER2 MBC. ONT-380 was administered twice daily (BID) in continuous 28-day cycles. After a modified 3+3 dose-escalation design determined the MTD, the expansion cohort was enrolled. PK properties of ONT-380 and a metabolite were determined. Response was evaluated by Response Evaluation Criteria in Solid Tumors (RECIST). Fifty patients received ONT-380 (escalation = 33; expansion = 17); 43 patients had HER2 MBC. Median prior anticancer regimens = 5. Dose-limiting toxicities of increased transaminases occurred at 800 mg BID, thus 600 mg BID was the MTD. Common AEs were usually Grade 1/2 in severity and included nausea (56%), diarrhea (52%), fatigue (50%), vomiting (40%) constipation, pain in extremity and cough (20% each). 5 patients (19%) treated at MTD had grade 3 AEs (increased transaminases, rash, night sweats, anemia, and hypokalemia). The half-life of ONT-380 was 5.38 hours and increases in exposure were approximately dose proportional. In evaluable HER2 MBC ( = 22) treated at doses ≥ MTD, the response rate was 14% [all partial response (PR)] and the clinical benefit rate (PR + stable disease ≥ 24 weeks) was 27%. ONT-380 had a lower incidence and severity of diarrhea and rash than that typically associated with current dual HER2/EGFR inhibitors and showed notable antitumor activity in heavily pretreated HER2 MBC patients, supporting its continued development. .

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Targeted therapy in HER2-positive breast cancer

Cited by 45 publications

References 72 publications

Clinical significance of sunitinib‐associated macrocytosis in metastatic renal cell carcinoma

Clinical significance of sunitinib‐associated macrocytosis in metastatic renal cell carcinoma

Increased gene copy number of HER2 and concordant protein overexpression found in a subset of eyelid sebaceous gland carcinoma indicate HER2 as a potential therapeutic target

Phase I Study of ONT-380, a HER2 Inhibitor, in Patients with HER2+-Advanced Solid Tumors, with an Expansion Cohort in HER2+ Metastatic Breast Cancer (MBC)

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