Abstract P4-12-24: Phase I trial of S-222611, a dual tyrosine kinase inhibitor of EGFR and HER2, with preliminary evidence of efficacy in patients (pts) with heavily-pretreated HER2-positive metastatic breast cancer

Author(s):  
RD Baird ◽  
N Cresti ◽  
E Beddowes ◽  
M Saggese ◽  
M Flynn ◽  
...  
ABOUTOPEN ◽  
2018 ◽  
Vol 4 (1) ◽  
pp. 66-68
Author(s):  
Daniela Cianniello ◽  
Roberta Caputo

Lapatinib is an intracellular tyrosine kinase inhibitor of EGFR (ErbB1) and HER2 (ErbB2) receptors, approved for the treatment of metastatic breast carcinoma pre-treated with anti-HER2 antibodies. We report the case of a 60-year-old woman diagnosed with metastatic breast neoplasm, HER2-positive, progressing after treatment with trastuzumab, pertuzumab and T-DM1, who obtained a regression of hepatic metastases after treatment with lapatinib-capecitabine (Oncology).


2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e11577-e11577 ◽  
Author(s):  
Javier Salvador ◽  
Manuel Ruiz Borrego ◽  
Maria Valero ◽  
Juan L. Bayo ◽  
Luis De La Cruz-Merino ◽  
...  

e11577 Background: The anti-HER2 monoclonal antibody trastuzumab and the tyrosine kinase inhibitor lapatinib have complementary mechanisms of action and synergistic antitumour activity in models of HER2-overexpressing breast cancer.In heavily pre-treated pts, L+T is associated with improved outcomes compared to L alone and significantly improved progression-free survival (PFS), offering a chemotherapy-free option for patients with heavily pretreated human epidermal growth factor. (Kimberly L et al, 2012 JCO). Methods: We evaluated the safety and efficacy of L+T in patients with 1-4 prior (Median 3) lines of chemotherapy (CT) for HER2+ MBC.: 20 Pts with measurable, HER2+ MBC were eligible. Pts received every 3 weeks T (8 mg/kg loading then 6 mg/Kg) and daily L 1000 mg. Results: The characteristic of the all of pts included (20) are: median age 51.4 (32-68) Total number of cycles administered was 141. The median cycles administered per pts was 6 (range 1-18). Median follow-up was 6 months. Of the 18 pts with response assessment, the clinical benefit obtained was: 76,1% (5,9% PR + and 70,6% disease stabilization) with 95% CI 71.3%-80.9%. Disease progression was 17,6%. Of the 20 pts with a median follow up of 13,32 m (3-32), median PFS for these pts was 6 m. The one year OS % was 64,70% (56,7-72,7). All pts had received al least one line lapatinib prior (1-3). Toxicity was generally manageable. No major cardiac dysfunctions ocurred. Grade 3/4 treatment-related toxicities were uncommon (grade 3 diarrhea, 18%; grade 3 hepatic 7%. All others < 3 %). Conclusions: L+T is an active regimen in HER2+ MBC. L+T showed high clinical benefit with manageable safety profile. Dual inhibition of HER2 might be a valid approach to treatment of Her-2 positive metastatic breast cancer.


2018 ◽  
Vol 36 (15_suppl) ◽  
pp. 1014-1014 ◽  
Author(s):  
Cristina Saura ◽  
Fiona Thistlethwaite ◽  
Udai Banerji ◽  
Simon Lord ◽  
Victor Moreno ◽  
...  

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e11515-e11515
Author(s):  
Katia Cagossi ◽  
Giorgia Razzini ◽  
Alessia Ferrari ◽  
Maria Grazia Lazzaretti ◽  
Meri Leporati ◽  
...  

e11515 Background: Current therapeutic goals for MBC, as an incurable disease, are symptoms and prolonged disease control together with good quality of life. Metronomic chemotherapy has shown efficacy in patients with metastatic breast cancer. We evaluated the efficacy and tolerability of the combination of anti-angiogenetic activity of metronomic chemotherapy with a tyrosine kinase inhibitor such as lapatinib in heavily pre-treated MBC HER-2 positive patients. Methods: Metastatic breast cancer patients HER-2 positive with CEA or Ca15.3 elevated, prior systemic therapy for advanced disease, ECOG performance status < 1 and life expectancy longer than 3 months. MBC patients were treated with metronomic oral capecitabine (1500 mg daily) and cyclophosphamide (50 mg daily) plus lapatinib (1250 mg daily). The treatment was given until disease progression. Primary objective was time to progression (TTP) and safety. Results: Fifteenpatients were included. Median age was 52 years old (range 42-77). Median number of previous chemotherapy lines was 5 (range 2-10). Median time to tumor progression was 6 months (2-14). No complete response was observed. Eight out of fiftten patients (60%) with pre-existing only bone metastases achieved a stable disease and/or partial response and were still on treatment after 6 month of therapy. At the same time 100% of these patients exhibited significant reduction of serum marker concentrations. No grade 3-4 skin toxicity was reported. Hematological and gastro-intestinal toxicity was well tolerated (G1-2). No reduction of dose was needed. Conclusions: The combination of lapatinib with metronomic chemotherapy may lead to effective palliation despite extensive pretreatment at least in bone metastatic patients. The treatment appears to be less toxic than lapatinib and capecitabine at full dosage, especially in heavily pretreated MBC patients. The preliminary results suggest the need of a clinical trial to confirm a role of this combination to delay lapatinib resistance.


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