A phase II trial of pan-HER inhibitor Poziotinib, in patients with HER2-positive metastatic breast cancer who have received at least two prior HER2-directed regimens: The results of NOV120101-203 trial

Park, Y.H.; Kh, Lee; Sohn, JH; Lee, K.S.; Jung, Kyung Hae; Kim, J.H.; Lee, K.H.; Ahn, Jin Seok; Ty, Kim; Kim, G.M.; Park, I.H.; Kim, SB; Kim, S.H.; Han, Hye Sook; Im, Y-H.; Ahn, Junseong; Jy, Kim; Kang, Jahoon; Im, Sungbin

doi:10.1093/annonc/mdx365.001

Cited by 2 publications

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“…12 An open-label, multicenter, phase II clinical trial of poziotinib for refractory HER2-positive BC patients who had failed more than two HER2 targeted therapies (NCT02418689) demonstrated a median 4.04 month PFS following poziotinib treatment after HER2 targeted treatment failure. 13 Our study showed that poziotinib was associated with similar efficacy in progression across patient subgroups predefined by age, visceral disease, previous treatment, and hormone receptor status. Only adverse events including diarrhea and skin rash would predict BC response to poziotinib.…”

Section: Introductionmentioning

confidence: 52%

Molecular alterations and poziotinib efficacy, a pan‐HER inhibitor, in human epidermal growth factor receptor 2 (HER2)‐positive breast cancers: Combined exploratory biomarker analysis from a phase II clinical trial of poziotinib for refractory HER2‐positive breast cancer patients

Kim

Lee

Park

et al. 2019

Intl Journal of Cancer

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We aimed to investigate the impact of genetic alterations on the efficacy of poziotinib in a phase II clinical trial of patients with heavily treated HER2-positive metastatic breast cancer (BC). We performed targeted ultra-deep sequencing with a customized cancer gene panel and RNA expression assay using BC specimens. Of 106 patients, biomarker data were available for 85. Copy number (CN) amplifications of HER2 were observed in 72 patients (85%), and CN >8 in 50 (59%). Single nucleotide variants (SNVs) of HER2 were found in 16 patients (19%). Genetic alterations of PIK3CA pathway were found in 40 patients (47%). Median progression free survival (PFS) of the biomarker analysis group was 3.61 months. In terms of PFS, HER2 with CN >8 prolonged (hazard ratio (HR) 0.61, 95% CI: 0.38, 0.97, p = 0.037) and alteration of PIK3CA pathway shortened the duration of survival (HR 2.25, 95% CI: 1.39, 3.63, p = 0.001). SNVs of HER2 increased survival duration, but the effect was not significant (HR: 0.58, 95% CI: 0.31, 1.08, p = 0.085). In addition, SNVs in the ERBB3 cytoplasmic domain decreased poziotinib response (HR: 4.58, 95% CI: 2.02, 10.37, p < 0.001). In multigene analysis, BC with HER2 CN >8 and intact PIK3CA pathway had significantly longer PFS compared to others (HR: 0.37, 95% CI: 0.21, 0.66, p = 0.001), while SNVs in the ERBB3 cytoplasmic domain predicted poor prognosis (HR: 4.28, 95% CI: 1.71, 10.71, p < 0.001). In conclusion, HER2 CN amplification, PIK3CA pathway alteration, and ERBB3 cytoplasmic mutation showed predictive roles on clinical outcomes of HER2-positive MBC treated with poziotinib.

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Section: Introductionmentioning

confidence: 52%

Molecular alterations and poziotinib efficacy, a pan‐HER inhibitor, in human epidermal growth factor receptor 2 (HER2)‐positive breast cancers: Combined exploratory biomarker analysis from a phase II clinical trial of poziotinib for refractory HER2‐positive breast cancer patients

Kim

Lee

Park

et al. 2019

Intl Journal of Cancer

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Trastuzumab Deruxtecan for HER2+ Advanced Breast Cancer

Lee

Park

2021

Future Oncol.

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Trastuzumab deruxtecan (T-DXd, DS-8201), an anti-HER2 antibody–drug conjugate, has shown significant clinical benefits in HER2+ metastatic breast cancer patients. In the phase 2 DESTINY-Breast01 trial, T-DXd demonstrated an objective response of 60.9% and median progression-free survival of 16.4 months, laying the foundation for accelerated approval in HER2+ metastatic breast cancer patients who have received two or more prior anti-HER2-based regimens in the metastatic setting. Moreover, T-DXd exhibited promising antitumor efficacy against HER2-low-expressing metastatic breast cancer. Its distinctive side effect was pneumonitis, with a 13.6% incidence. It is approved in the US with boxed warnings for interstitial lung disease and embryo–fetal toxicity. This review focuses on preclinical, pharmacokinetic and pharmacodynamic data on T-DXd and clinical evidence of its antitumor activity (both as monotherapy and in combination) and tolerability in metastatic breast cancer.

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A phase II trial of pan-HER inhibitor Poziotinib, in patients with HER2-positive metastatic breast cancer who have received at least two prior HER2-directed regimens: The results of NOV120101-203 trial

Cited by 2 publications

References 0 publications

Molecular alterations and poziotinib efficacy, a pan‐HER inhibitor, in human epidermal growth factor receptor 2 (HER2)‐positive breast cancers: Combined exploratory biomarker analysis from a phase II clinical trial of poziotinib for refractory HER2‐positive breast cancer patients

Molecular alterations and poziotinib efficacy, a pan‐HER inhibitor, in human epidermal growth factor receptor 2 (HER2)‐positive breast cancers: Combined exploratory biomarker analysis from a phase II clinical trial of poziotinib for refractory HER2‐positive breast cancer patients

Trastuzumab Deruxtecan for HER2+ Advanced Breast Cancer

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