Cristina Oliva

Bio: Cristina Oliva is an academic researcher from Takeda Pharmaceutical Company. The author has contributed to research in topics: Lapatinib & Breast cancer. The author has an hindex of 23, co-authored 47 publications receiving 7848 citations. Previous affiliations of Cristina Oliva include GlaxoSmithKline & University of Southern California.

Lapatinib plus Capecitabine for HER2-Positive Advanced Breast Cancer

Abstract: A b s t r ac t The interim analysis of time to progression met specified criteria for early reporting on the basis of superiority in the combination-therapy group. The hazard ratio for the independently assessed time to progression was 0.49 (95% confidence interval, 0.34 to 0.71; P<0.001), with 49 events in the combination-therapy group and 72 events in the monotherapy group. The median time to progression was 8.4 months in the combination-therapy group as compared with 4.4 months in the monotherapy group. This improvement was achieved without an increase in serious toxic effects or symptomatic cardiac events. Conclusions Lapatinib plus capecitabine is superior to capecitabine alone in women with HER2- positive advanced breast cancer that has progressed after treatment with regimens that included an anthracycline, a taxane, and trastuzumab. (ClinicalTrials.gov number, NCT00078572.)

Lapatinib Combined With Letrozole Versus Letrozole and Placebo As First-Line Therapy for Postmenopausal Hormone Receptor–Positive Metastatic Breast Cancer

Abstract: Purpose Cross-talk between human epidermal growth factor receptors and hormone receptor pathways may cause endocrine resistance in breast cancer. This trial evaluated the effect of adding lapatinib, a dual tyrosine kinase inhibitor blocking epidermal growth factor receptor and human epidermal growth factor receptor 2 (HER2), to the aromatase inhibitor letrozole as first-line treatment of hormone receptor (HR) –positive metastatic breast cancer (MBC). Patients and Methods Postmenopausal women with HR-positive MBC were randomly assigned to daily letrozole (2.5 mg orally) plus lapatinib (1,500 mg orally) or letrozole and placebo. The primary end point was progression-free survival (PFS) in the HER2-positive population. Results In HR-positive, HER2-positive patients (n 219), addition of lapatinib to letrozole significantly reduced the risk of disease progression versus letrozole-placebo (hazard ratio [HR] 0.71; 95% CI, 0.53 to 0.96; P .019); median PFS was 8.2 v 3.0 months, respectively. Clinical benefit (responsive or stable disease 6 months) was significantly greater for lapatinib-letrozole versus letrozole-placebo (48% v 29%, respectively; odds ratio [OR] 0.4; 95% CI, 0.2 to 0.8; P .003). Patients with centrally confirmed HR-positive, HER2-negative tumors (n 952) had no improvement in PFS. A preplanned Cox regression analysis identified prior antiestrogen therapy as a significant factor in the HER2-negative population; a nonsignificant trend toward prolonged PFS for lapatinib-letrozole was seen in patients who experienced relapse less than 6 months since prior tamoxifen discontinuation (HR 0.78; 95% CI, 0.57 to 1.07; P .117). Grade 3 or 4 adverse events were more common in the lapatinib-letrozole arm versus letrozole-placebo arm (diarrhea, 10% v 1%; rash, 1% v 0%, respectively), but they were manageable.

A phase III randomized comparison of lapatinib plus capecitabine versus capecitabine alone in women with advanced breast cancer that has progressed on trastuzumab: updated efficacy and biomarker analyses

Abstract: Purpose Lapatinib is a small molecule, dual tyrosine kinase inhibitor of epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor type 2 (HER2). Initial results of a phase III trial demonstrated that lapatinib plus capecitabine is superior to capecitabine alone in women with HER2-positive advanced breast cancer that progressed following prior therapy including trastuzumab. Updated efficacy and initial biomarker results from this trial are reported. Methods Women with HER2-positive, locally advanced or metastatic breast cancer previously treated with anthracycline-, taxane-, and trastuzumab-containing regimens were randomized to lapatinib 1,250 mg/day continuously plus capecitabine 2,000 mg/m2 days 1–14 of a 21-day cycle or capecitabine 2,500 mg/m2 on the same schedule. The primary endpoint was time to progression (TTP) as determined by an independent review panel. Relationship between progression-free survival (PFS) and tumor HER2 expression and serum levels of HER2 extracellular domain (ECD) were assessed. Results 399 women were randomized. The addition of lapatinib prolonged TTP with a hazard ratio (HR) of 0.57 (95% CI, 0.43–0.77; P < 0.001) and provided a trend toward improved overall survival (HR: 0.78, 95% CI: 0.55–1.12, P = 0.177), and fewer cases with CNS involvement at first progression (4 vs. 13, P = 0.045). Baseline serum HER2 ECD did not predict for benefit from lapatinib. Conclusion The addition of lapatinib to capecitabine provides superior efficacy for women with HER2-positive, advanced breast cancer progressing after treatment with anthracycline-, taxane-, and trastuzumab-based therapy. Biomarker studies could not identify a subgroup of patients who failed to benefit from the addition of lapatinib to capecitabine.

Multicenter Phase II Study of Lapatinib in Patients with Brain Metastases from HER2-Positive Breast Cancer

Abstract: Purpose: Brain metastases develop in one third of patients with advanced HER2+ breast cancer. Effective therapy for patients with central nervous system (CNS) progression after cranial radiation is extremely limited and represents a major clinical challenge. Lapatinib, an epidermal growth factor receptor/HER2 inhibitor, was associated with regressions of CNS lesions in a small phase 2 trial. The current study was done to further evaluate the CNS activity of lapatinib. The study was later amended to allow patients who progressed on lapatinib the option of receiving lapatinib plus capecitabine. Experimental Design: Eligible patients had HER2+ breast cancer, progressive brain metastases, prior trastuzumab, and cranial radiotherapy. The primary end point was CNS objective response, defined as ≥50% volumetric reduction of CNS lesion(s) in the absence of increasing steroid use, progressive neurologic signs and symptoms, or progressive extra-CNS disease. Results: Two-hundred and forty-two patients entered the study. CNS objective responses to lapatinib were observed in 6% of patients. In an exploratory analysis, 21% of patients experienced a ≥20% volumetric reduction in their CNS lesions. An association was observed between volumetric reduction and improvement in progression-free survival and neurologic signs and symptoms. Of the 50 evaluable patients who entered the lapatinib plus capecitabine extension, 20% experienced a CNS objective response and 40% experienced a ≥20% volumetric reduction in their CNS lesions. Conclusions: This study confirms the modest CNS antitumor activity of lapatinib. Additional responses were observed with the combination of lapatinib and capecitabine. Further studies of lapatinib-based regimens for CNS metastases from HER2+ breast cancer are warranted.

Identification of human triple-negative breast cancer subtypes and preclinical models for selection of targeted therapies

Abstract: Triple-negative breast cancer (TNBC) is a highly diverse group of cancers, and subtyping is necessary to better identify molecular-based therapies. In this study, we analyzed gene expression (GE) profiles from 21 breast cancer data sets and identified 587 TNBC cases. Cluster analysis identified 6 TNBC subtypes displaying unique GE and ontologies, including 2 basal-like (BL1 and BL2), an immunomodulatory (IM), a mesenchymal (M), a mesenchymal stem–like (MSL), and a luminal androgen receptor (LAR) subtype. Further, GE analysis allowed us to identify TNBC cell line models representative of these subtypes. Predicted “driver” signaling pathways were pharmacologically targeted in these cell line models as proof of concept that analysis of distinct GE signatures can inform therapy selection. BL1 and BL2 subtypes had higher expression of cell cycle and DNA damage response genes, and representative cell lines preferentially responded to cisplatin. M and MSL subtypes were enriched in GE for epithelial-mesenchymal transition, and growth factor pathways and cell models responded to NVP-BEZ235 (a PI3K/mTOR inhibitor) and dasatinib (an abl/src inhibitor). The LAR subtype includes patients with decreased relapse-free survival and was characterized by androgen receptor (AR) signaling. LAR cell lines were uniquely sensitive to bicalutamide (an AR antagonist). These data may be useful in biomarker selection, drug discovery, and clinical trial design that will enable alignment of TNBC patients to appropriate targeted therapies.

Fluorine in pharmaceutical industry: fluorine-containing drugs introduced to the market in the last decade (2001-2011).

Abstract: Introduced to the Market in the Last Decade (2001−2011) Jiang Wang,† María Sańchez-Rosello,́‡,§ Jose ́ Luis Aceña, Carlos del Pozo,‡ Alexander E. Sorochinsky, Santos Fustero,*,‡,§ Vadim A. Soloshonok,* and Hong Liu*,† †Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zu Chong Zhi Road, Shanghai 201203, China ‡Department of Organic Chemistry, Faculty of Pharmacy, University of Valencia, Av. Vicente Andreś Estelleś, 46100 Burjassot, Valencia, Spain Laboratorio de Molećulas Orgańicas, Centro de Investigacioń Príncipe Felipe, C/ Eduardo Primo Yuf́era 3, 46012 Valencia, Spain Department of Organic Chemistry I, Faculty of Chemistry, University of the Basque Country UPV/EHU, Paseo Manuel Lardizab́al 3, 20018 San Sebastian, Spain IKERBASQUE, Basque Foundation for Science, Alameda Urquijo, 36-5 Plaza Bizkaia, 48011 Bilbao, Spain Institute of Bioorganic Chemistry and Petrochemistry, National Academy of Sciences of Ukraine, Murmanska Street 1, 02660 Kyiv-94, Ukraine

Recommendations for human epidermal growth factor receptor 2 testing in breast cancer: American Society of Clinical Oncology/College of American Pathologists clinical practice guideline update.

Abstract: Purpose To update the American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guideline recommendations for human epidermal growth factor receptor 2 (HER2) testing in breast cancer to improve the accuracy of HER2 testing and its utility as a predictive marker in invasive breast cancer.

Trastuzumab Emtansine for HER2-Positive Advanced Breast Cancer

Abstract: Background Trastuzumab emtansine (T-DM1) is an antibody–drug conjugate incorporating the human epidermal growth factor receptor 2 (HER2)–targeted antitumor properties of tras tuz u mab with the cytotoxic activity of the microtubule-inhibitory agent DM1. The antibody and the cytotoxic agent are conjugated by means of a stable linker. Methods We randomly assigned patients with HER2-positive advanced breast cancer, who had previously been treated with tras tuz u mab and a taxane, to T-DM1 or la pa ti nib plus cap e ci ta bine. The primary end points were progression-free survival (as assessed by independent review), overall survival, and safety. Secondary end points included progression-free survival (investigator-assessed), the objective response rate, and the time to symptom progression. Two interim analyses of overall survival were conducted. Results Among 991 randomly assigned patients, median progression-free survival as assessed by independent review was 9.6 months with T-DM1 versus 6.4 months with la pa ti nib plus cap e ci ta bine (hazard ratio for progression or death from any cause, 0.65; 95% confidence interval [CI], 0.55 to 0.77; P<0.001), and median overall survival at the second interim analysis crossed the stopping boundary for efficacy (30.9 months vs. 25.1 months; hazard ratio for death from any cause, 0.68; 95% CI, 0.55 to 0.85; P<0.001). The objective response rate was higher with T-DM1 (43.6%, vs. 30.8% with la pa ti nib plus cap e ci ta bine; P<0.001); results for all additional secondary end points favored T-DM1. Rates of adverse events of grade 3 or above were higher with la pati nib plus cap e ci ta bine than with T-DM1 (57% vs. 41%). The incidences of thrombocytopenia and increased serum aminotransferase levels were higher with T-DM1, whereas the incidences of diarrhea, nausea, vomiting, and palmar–plantar erythro dysesthesia were higher with la pa ti nib plus cap e ci ta bine. Conclusions T-DM1 significantly prolonged progression-free and overall survival with less toxicity than la pa ti nib plus cap e ci ta bine in patients with HER2-positive advanced breast cancer previously treated with tras tuz u mab and a taxane. (Funded by F. Hoffmann– La Roche/Genentech; EMILIA ClinicalTrials.gov number, NCT00829166.)

Recommendations for Human Epidermal Growth Factor Receptor 2 Testing in Breast Cancer: American Society of Clinical Oncology/College of American Pathologists Clinical Practice Guideline Update

Abstract: Purpose.—To update the American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guideline recommendations for human epidermal growth factor receptor 2 (HER2) testing in b...