Abstract PD2-08: Neratinib + fulvestrant inERBB2-mutant, HER2–non-amplified, estrogen receptor (ER)-positive, metastatic breast cancer (MBC): Preliminary analysis from the phase II SUMMIT trial

2017 ◽  
Author(s):  
D Hyman ◽  
S Piha-Paul ◽  
C Saura ◽  
C Arteaga ◽  
I Mayer ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Metastatic Breast Cancer ◽  
Phase Ii ◽  
Preliminary Analysis ◽  
Metastatic Breast ◽  
Er Positive

scholarly journals Randomized phase-II evaluation of letrozole plus dasatinib in hormone receptor positive metastatic breast cancer patients

2019 ◽  
Vol 5 (1) ◽  
Author(s):  
Devchand Paul ◽  
Svetislava J. Vukelja ◽  
Frankie Ann Holmes ◽  
Joanne L. Blum ◽  
Kristi J. McIntyre ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Phase Ii ◽  
Kinase Inhibitor ◽  
Acquired Resistance ◽  
Metastatic Breast ◽  
Progression Free Survival ◽  
Therapy Resistance ◽  
Breast Cancer Patients ◽  
Er Positive

Abstract The non-receptor tyrosine kinase Src activation plays a role in the malignant progression of breast cancer, including development of endocrine therapy resistance and survival of bone metastases. This study investigated whether adding Src kinase inhibitor dasatinib to aromatase inhibitor (AI) therapy improved outcomes in estrogen receptor (ER)-positive, HER2-negative metastatic breast cancer (MBC). Postmenopausal patients with ER-positive, HER2-negative MBC (0–1 prior chemotherapies and no prior AI for MBC) were eligible for this non-comparative, parallel group, phase-II study. Patients were randomized to letrozole (2.5 mg/day PO) alone or with dasatinib (100 mg/day PO). Patients with disease progression on letrozole alone could crossover to dasatinib plus continued letrozole. The primary endpoint was clinical-benefit-rate (CBR; complete response + partial response + stable disease ≥6 months). A total of 120 patients were randomized. The CBR of 71% (95% CI 58–83%) was observed with letrozole + dasatinib versus the projected CBR of the combination of 56%. The CBR of 66% (95% CI 52–77%) with letrozole alone also exceeded the projected CBR of 39% with letrozole alone. The CBR was 23% in the crossover arm of letrozole plus dasatinib in patients progressing on letrozole alone. Median progression-free survival with the combination was 20.1 months and 9.9 months with letrozole alone. Letrozole plus dasatinib was well tolerated, although 26% of patients required dasatinib dose reductions. In this non-comparative phase-II trial, the CBR of 71% and the median PFS of 20.1 months with letrozole + dasatinib are encouraging and suggest that dasatinib may inhibit the emergence of acquired resistance to AI therapy.

First-line treatment of metastatic breast cancer with weekly abraxane (nab-paclitaxel: a 130 nm albumin-bound paclitaxel particle): A preliminary analysis of the phase II international oncology network ION-04–012 study

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 10707-10707 ◽  
Author(s):  
B. Mirtsching ◽  
T. Chidiac ◽  
T. Cosgriff
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Phase Ii ◽  
Preliminary Analysis ◽  
Metastatic Breast ◽  
Line Treatment ◽  
First Line ◽  
Grade 3 ◽  
First Line Treatment ◽  
Patient Accrual

10707 Background: Abraxane (paclitaxel protein-bound particles) by intravenous weekly administration schedule has been demonstrated to be active and well tolerated in patients with metastatic breast cancer (MBC) refractory to prior taxane therapy. The purpose of this Phase II, open-label, non-randomized study is to evaluate the efficacy and safety of Abraxane administered weekly to patients with locally-advanced unresectable breast cancer (LABC) or MBC as first-line treatment. Methods: Patients ≥ 18 years with histologically confirmed LABC or MBC received Abraxane (125 mg/m2) by 30 minute IV infusion on days 1, 8, and 15 for the first 3 weeks of each 4-week cycle. HER2-positive patients received concurrent Herceptin given weekly throughout therapy, 4 mg/kg on week 1, and 2 mg/kg on subsequent weeks. Results: From March 11, 2005 to January 4, 2006, 28 patients were enrolled and 27 received study medication (included in this preliminary analysis). Patient accrual continues. Patient characteristics included: gender (M/F) 0/27, median age 60.5 years (range 36–83), ECOG performance status (0–1) 13/14, and HER2 status (±/missing) 6/18/3. A total of 285 cycles have been administered (median 3 [range 1–8]) with a median dose of 125 mg/m2 (range 0–130 mg/m2) and 6 dose modifications have occurred due to toxicity. Eighteen patients are still on study. CTC hematologic toxicities were grade 3 leukopenia (3.7% of patients) and grade 3 neutropenia (7.4%). Grade 3 nonhematologic toxicities were gastritis (3.7%), peripheral sensory neuropathy (7.4%), arthralgia (3.7%), and bone pain (3.7%). No grade 4 nonhematologic toxicities occurred. Conclusions: Preliminary data show that Abraxane given weekly at 125 mg/m2 (with or without Herceptin) for first-line treatment of MBC is well tolerated. Patient accrual continues in this study. Updated analysis of this study will be provided at the meeting. No significant financial relationships to disclose.

Phase I Study of a Third-Generation Selective Estrogen Receptor Modulator, LY353381.HCl, in Metastatic Breast Cancer

2001 ◽  
Vol 19 (7) ◽  
pp. 2002-2009 ◽  
Author(s):  
Pamela N. Münster ◽  
Aman Buzdar ◽  
Kapil Dhingra ◽  
Nathan Enas ◽  
Lan Ni ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Metastatic Breast Cancer ◽  
Phase I ◽  
Metastatic Breast ◽  
Median Number ◽  
Third Generation ◽  
Receptor Modulator ◽  
Er Positive ◽  
Dose Levels

PURPOSE: We conducted this phase I trial to determine the safety and toxicity profile of LY353381.HCl—a novel, potent, third-generation selective estrogen receptor modulator (SERM)—because this benzothiophene derivative demonstrated an SERM profile in preclinical studies. PATIENTS AND METHODS: We studied 32 patients with recurrent or metastatic breast cancer. Patients were treated in four cohorts with oral daily doses of 10, 20, 50, and 100 mg. Pharmacokinetic sampling was performed during the first 72 hours following the first dose on day 1 and during the 24 hours after the day 57 dose. Eligibility criteria included Eastern Cooperative Oncology Group performance status of 0 to 2; no significant major organ dysfunction; and at least 3 weeks elapsed since most recent hormonal therapy, chemotherapy, and estrogen replacement therapy. RESULTS: The median patient age was 56 years (range, 30 years to 76 years). The median number of prior chemotherapies for metastatic disease was one (range, zero to four), while the median number of prior hormone regimens for metastatic disease was two (range, zero to five). Receptor status was estrogen receptor (ER) positive and progesterone receptor (PR) positive, 19 patients; ER positive and PR negative, eight patients; ER positive and PR unknown, two patients; and ER and PR unknown, three patients. Dose-limiting toxicity was not observed. Treatment was well tolerated with mild to moderate hot flashes in 18 of 32 patients (56%) at all dose levels. Transvaginal ultrasound performed at baseline and after 12 weeks of treatment showed no endometrial thickening. Of the 32 patients evaluable for response, six patients had stable disease for at least 6 months with a median duration of 7.7 months (range, 6.2 months to 33.8 months). The pharmacokinetics of LY353381.HCl were generally linear with respect to time and studied dose range. CONCLUSION: As predicted in preclinical testing, daily oral LY353381.HCl is safe, is well tolerated at all tested dose levels, and may be clinically beneficial in patients with extensively pretreated metastatic breast cancer. Further studies with LY353381 to evaluate the efficacy in patients with or without prior exposure to tamoxifen and fewer overall prior regimens are under way.

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