Lapatinib-associated mucocutaneous toxicities are clinical predictors of improved progression-free survival in patients with human epidermal growth factor receptor (HER2)-positive advanced breast cancer

Araki, Kazuhiro; Fukada, Ippei; Horii, Rie; Takahashi, Shunji; Akiyama, Futoshi; Iwase, Takuji; Ito, Yoshiaki

doi:10.1007/s10549-014-3148-7

Cited by 6 publications

(3 citation statements)

References 52 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Preliminary evidence indicates that early lapatinib plus capecitabine induced AE may be associated with improved survival outcomes. For example, lapatinib plus capecitabine induced rash, hand foot syndrome and diarrhoea have been associated with improved PFS in a small cohort of 76 HER2-positive ABC patients [9]. Early lapatinib-related rash (within 42 days) has been significantly associated with OS and a trend towards improved disease free survival in a cohort of 3973 HER2-positive early breast cancer patients receiving adjuvant therapy [10].…”

Section: Ivyspring International Publishermentioning

confidence: 99%

Early Adverse Events predict Survival Outcomes in HER2-positive Advanced Breast Cancer Patients treated with Lapatinib plus Capecitabine

Ang¹,

Rowland²,

Modi³

et al. 2020

J. Cancer

View full text Add to dashboard Cite

Background: This study aimed to investigate the impact of early adverse events (AE) following the initiation of lapatinib plus capecitabine on the progression-free survival (PFS) and overall survival (OS) outcomes of human epidermal growth factor receptor 2 (HER2) positive advanced breast cancer (ABC) patients. Methods: A secondary analysis of participants treated with lapatinib plus capecitabine, or ado-trastuzumab emtansine in the clinical trial EMILIA was conducted. Cox proportional hazard analysis was used to assess the impact of AE occurring within the first 42 days of lapatinib plus capecitabine therapy on the PFS and OS outcomes of ABC patients. Results: The study included 488 HER2-positive (ABC) patients initiated on lapatinib plus capecitabine. Rash (Hazard Ratio (HR) [95% Confidence Interval (CI)]: Grade 1 = 0.67 [0.46-0.98], Grade 2+ = 0.71 [0.42-1.19]; p = 0.046) and hand-foot syndrome (HR [95% CI]: Grade 1 = 0.58 [0.43-0.80], Grade 2+ = 0.61 [0.43-0.86]; p = <0.001) occurring within the first 42 days of lapatinib plus capecitabine therapy were significantly associated with improved OS. Conversely, nausea and vomiting occurring within the first 42 days of lapatinib plus capecitabine therapy was significantly associated with worsened OS (HR [95% CI]: Grade 1 = 1.08 [0.82-1.42], Grade 2+ = 1.52 [1.13-2.03]; p = 0.027).Conclusions: Rash and hand-foot syndrome occurring early after the initiation of on lapatinib plus capecitabine were significantly associated with improved OS, while early nausea and vomiting was associated with worse OS. In HER2-positive ABC patients initiating lapatinib plus capecitabine, consideration should be given to more closely monitoring patients at risk of nausea and vomiting, while rash and hand foot syndrome are AE associated with improved survival.

show abstract

Section: Ivyspring International Publishermentioning

confidence: 99%

Early Adverse Events predict Survival Outcomes in HER2-positive Advanced Breast Cancer Patients treated with Lapatinib plus Capecitabine

Ang¹,

Rowland²,

Modi³

et al. 2020

J. Cancer

View full text Add to dashboard Cite

show abstract

“…Lapatinib is an oral drug that inhibits the tyrosine kinases of HER2 and epidermal growth factor receptor type 1 (EGFR) and has demonstrated clinical activity in trastuzumab‐refractory states . Lapatinib has also shown clinical activity in IBC, but evidence in this field is scarce …”

Section: Clinical Trials Of Lapatinib In Inflammatory Breast Cancer Amentioning

confidence: 99%

“…About toxicity, our patient had limitant dose toxicity. In some studies, lapatinib‐associated mucocutaneous toxicities have been proposed as predictors of improved progression‐free survival in HER2‐positive IBC patients, but we do not know the repercussion of this aspect yet …”

Section: Clinical Trials Of Lapatinib In Inflammatory Breast Cancer Amentioning

confidence: 99%

Early relapse of inflammatory breast carcinoma treated with lapatinib and capecitabine: Ten years of complete response

et al. 2019

View full text Add to dashboard Cite

Inflammatory breast carcinoma (IBC) is a rare form of breast cancer characterized by a rapid onset of diffuse skin erythema, edema, induration, and warmth of the breast. Biologically, IBC is usually hormone receptor (HR) negative and experience an overexpression of human epidermal growth factor receptor 2 (HER2), with a high mitotic index (MIB-1 > 20%). Median overall survival is poor. 1Lapatinib is an oral drug that inhibits the tyrosine kinases of HER2 and epidermal growth factor receptor type 1 (EGFR) and has demonstrated clinical activity in trastuzumab-refractory states. 2 Lapatinib has also shown clinical activity in IBC, but evidence in this field is scarce. [3][4][5][6][7][8][9] We present the case of an approximately ten-year maintained complete response using lapatinib and capecitabine to treat an IBC early relapse after trastuzumab treatment.A 34-year-old woman was diagnosed with multifocal invasive ductal carcinoma of the right breast (grade III). The immunohistochemical study showed the lesion tested negative for HR and positive for HER2 protein expression (3+). MIB-1 expression was high, more than 25%, and a strong nuclear P53 expression was established. The patient was diagnosed with locally advanced breast cancer (cT2cN1M0).In April 2007, neo-adjuvant chemotherapy was initiated using doxorubicin plus cyclophosphamide during four cycles, followed byThis is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

show abstract

Identification and characterization of biomarkers and their functions for Lapatinib-resistant breast cancer

Zhang

Huang

et al. 2017

Med Oncol

View full text Add to dashboard Cite

Lapatinib, a novel oral dual tyrosine kinase inhibitor blocking HER1 and HER2 pathways, has presented beneficial effects on breast cancer with positive HER2. However, its efficacy is largely limited by the occurrence of acquired drug resistance. In this study, we aimed to explore the underlying molecular mechanisms of Lapatinib resistance using bioinformatics strategies. The gene expression profile of SKBR3-R (acquired Lapatinib-resistant) and SKBR3 (Lapatinib-sensitive) cell line was downloaded from gene expression omnibus database. Then, the differentially expressed genes (DEGs) were selected using dChip software. Furthermore, gene ontology (GO) and pathway enrichment analyses were carried out by using DAVID database. Finally, the protein-protein interaction network was constructed, and the hub genes in the network were analyzed by using STRING database. A total of 300 DEGs, such as HSPA5, MAP1LC3A and RASSF2, were screened out. GO functional enrichment analysis showed that the genes were associated with cell membrane component-related, stimulus-related and binding-related items. KEGG pathway analysis indicated that three dysfunctional pathways, including PPAR signaling pathway, cytokine-cytokine receptor interaction and pathways in cancer, were enriched. Protein-protein interaction network construction revealed that some hub genes, such as PPARG, TGFBI, TGFBR2, TIMP1, CTGF, UBA52 and JUN, might have an association with Lapatinib resistance. The present study offered new insights into the molecular mechanisms of Lapatinib resistance and identified a series of important hub genes that have the potential to be the targets for treatment of Lapatinib-resistant breast cancer.

show abstract

Lapatinib-associated mucocutaneous toxicities are clinical predictors of improved progression-free survival in patients with human epidermal growth factor receptor (HER2)-positive advanced breast cancer

Cited by 6 publications

References 52 publications

Early Adverse Events predict Survival Outcomes in HER2-positive Advanced Breast Cancer Patients treated with Lapatinib plus Capecitabine

Early Adverse Events predict Survival Outcomes in HER2-positive Advanced Breast Cancer Patients treated with Lapatinib plus Capecitabine

Early relapse of inflammatory breast carcinoma treated with lapatinib and capecitabine: Ten years of complete response

Identification and characterization of biomarkers and their functions for Lapatinib-resistant breast cancer

Contact Info

Product

Resources

About