Poziotinib Treatment in Patients With HER2-Positive Advanced Breast Cancer Who Have Received Prior anti-HER2 Regimens
Abstract Purpose 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 and Methods Patients who had received at least two prior HER2-directed therapy lines for advanced disease, received 24mg poziotinib on an intermittent dosing schedule (cohort 1) or 16mg 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. Results 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. Conclusion Poziotinib demonstrated encouraging evidence of clinical activity in patients with pre-treated HER2-positive advanced breast cancer and merits further evaluation in additional studies. ClinicalTrials.gov Identifier: NCT02659514.
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Preprint| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
ResearchSquare.com - (2024) vom: 29. Jan. Zur Gesamtaufnahme - year:2024 |
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| Sprache: |
Englisch |
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| Beteiligte Personen: |
Nasrazadani, Azadeh [VerfasserIn] |
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| doi: |
10.21203/rs.3.rs-2956429/v1 |
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| 520 | |a Abstract Purpose 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 and Methods Patients who had received at least two prior HER2-directed therapy lines for advanced disease, received 24mg poziotinib on an intermittent dosing schedule (cohort 1) or 16mg 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. Results 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. Conclusion Poziotinib demonstrated encouraging evidence of clinical activity in patients with pre-treated HER2-positive advanced breast cancer and merits further evaluation in additional studies. ClinicalTrials.gov Identifier: NCT02659514 | ||
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