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type=\u0022text\/css\u0022 rel=\u0022stylesheet\u0022 href=\u0022\/\/d282kpwvnogo5m.cloudfront.net\/sites\/default\/files\/advagg_css\/css__ce2QY63WIanKyr8eSq7eavr1XQRRmFD6ZSmwpyJi8lM__zXwFqpqmxrZOXXcd_TpBQpjuELbmIP9wBR5UuTDWAO4__YJWWMMdfCJuAFm5cUEp88OsodhO3ZA-2lzRfoBsSlk4.css\u0022 media=\u0022all\u0022 \/\u003E\n\u003Clink rel=\u0027stylesheet\u0027 type=\u0027text\/css\u0027 href=\u0027\/sites\/all\/modules\/contrib\/panels\/plugins\/layouts\/onecol\/onecol.css\u0027 \/\u003E\u003C\/head\u003E\u003Cbody\u003E\u003Cdiv class=\u0022panels-ajax-tab-panel panels-ajax-tab-panel-sageoa-tab-art\u0022\u003E\u003Cdiv class=\u0022panel-display panel-1col clearfix\u0022 \u003E\n  \u003Cdiv class=\u0022panel-panel panel-col\u0022\u003E\n    \u003Cdiv\u003E\u003Cdiv class=\u0022panel-pane pane-highwire-markup\u0022 \u003E\n  \n      \n  \n  \u003Cdiv class=\u0022pane-content\u0022\u003E\n    \u003Cdiv class=\u0022highwire-markup\u0022\u003E\u003Cdiv xmlns=\u0022http:\/\/www.w3.org\/1999\/xhtml\u0022 id=\u0022content-block-markup\u0022 xmlns:xhtml=\u0022http:\/\/www.w3.org\/1999\/xhtml\u0022\u003E\u003Cdiv class=\u0022article fulltext-view \u0022\u003E\u003Cspan class=\u0022highwire-journal-article-marker-start\u0022\u003E\u003C\/span\u003E\u003Cdiv class=\u0022section abstract\u0022 id=\u0022abstract-1\u0022\u003E\u003Ch2\u003ESummary\u003C\/h2\u003E\u003Cp id=\u0022p-1\u0022\u003EThe BOLERO-1 phase 3 clinical trial demonstrated that adding everolimus to weekly trastuzumab and paclitaxel, as first-line therapy, did not improve progression-free survival in women with previously untreated human epidermal growth factor receptor-2-positive advanced breast cancer. PFS was increased by 7 months with everolimus therapy in the HR-negative subgroup; however, this did not cross the statistical significance threshold. Increased adverse events were also reported in the everolimus-treated group, as well as on treatment, AE-related deaths.\u003C\/p\u003E\u003C\/div\u003E\u003Cul class=\u0022kwd-group\u0022\u003E\u003Cli class=\u0022kwd\u0022\u003Ecombination treatment\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003Eprogression-free survival\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003Emetastatic breast cancer\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003Elocally advanced breast cancer\u003C\/li\u003E\u003C\/ul\u003E\u003Cul class=\u0022kwd-group drug\u0022\u003E\u003Cli class=\u0022kwd\u0022\u003Eeverolimus\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003Etrastuzumab\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003Epaclitaxel\u003C\/li\u003E\u003C\/ul\u003E\u003Cul class=\u0022kwd-group clinical-trial\u0022\u003E\u003Cli class=\u0022kwd\u0022\u003EEverolimus in Combination With Trastuzumab and Paclitaxel in the Treatment of HER2 Positive Locally Advanced or Metastatic Breast Cancer\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003EBOLERO-1\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003ENCT00876395\u003C\/li\u003E\u003C\/ul\u003E\u003Cdiv class=\u0022section\u0022 id=\u0022sec-1\u0022\u003E\u003Cp id=\u0022p-2\u0022\u003ESara A. Hurvitz, MD, University of California at Los Angeles, Los Angeles, California, USA, shared data from the Everolimus in Combination With Trastuzumab and Paclitaxel in the Treatment of HER2 Positive Locally Advanced or Metastatic Breast Cancer trial [BOLERO-1; \u003Ca class=\u0022external-ref external-ref-type-clintrialgov\u0022 href=\u0022\/lookup\/external-ref?link_type=CLINTRIALGOV\u0026amp;access_num=NCT00876395\u0026amp;atom=%2Fspmdc%2F14%2F56%2F11.atom\u0022\u003ENCT00876395\u003C\/a\u003E]. The data showed that adding everolimus to combination trastuzumab and paclitaxel therapy did not improve progression-free survival (PFS) in women with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (BC).\u003C\/p\u003E\u003Cp id=\u0022p-3\u0022\u003EResistance to trastuzumab remains a significant challenge in the treatment of HER2-positive BC, said Dr Hurvitz, adding that hyperactivation of the phosphoinositide-3 kinase\/mammalian target of rapamycin (mTOR) pathway has been implicated in this resistance [Hurvitz SA et al. \u003Cem\u003ECancer Treat Rev.\u003C\/em\u003E 2013], and mTOR inhibitors have shown some potential to increase PFS in this patient population [Andr\u00e9 F et al. \u003Cem\u003ELancet Oncol\u003C\/em\u003E. 2014].\u003C\/p\u003E\u003Cp id=\u0022p-4\u0022\u003EThe phase 3 BOLERO-1 trial was subsequently conducted in patients (n\u2009=\u2009719) with locally advanced or metastatic HER2-positive BC who had received no prior therapy (other than endocrine therapy, prior adjuvant or neoadjuvant trastuzumab therapy, or chemotherapy). Participants were randomized 2:1 to receive everolimus (10 mg PO daily) plus weekly paclitaxel and trastuzumab, or placebo plus weekly paclitaxel and trastuzumab. Treatment continued to the point of disease progression or intolerable toxicity.\u003C\/p\u003E\u003Cp id=\u0022p-5\u0022\u003EThe primary end point was PFS in the entire study population and in a hormone receptor\u2013negative subgroup of patients. Secondary end points included overall response rate (ORR), clinical benefit rate (CBR), and safety.\u003C\/p\u003E\u003Cp id=\u0022p-6\u0022\u003EAt the time of the final analysis, performed after 425 PFS events in the entire study population, there was no significant difference in median PFS between the everolimus and placebo arms (14.95 vs 14.49 months; HR, 0.89; 95% CI, 0.73 to 1.08; log-rank \u003Cem\u003EP\u003C\/em\u003E\u2009=\u2009.1166; \u003Ca id=\u0022xref-fig-1-1\u0022 class=\u0022xref-fig\u0022 href=\u0022#F1\u0022\u003EFigure 1\u003C\/a\u003E).\u003C\/p\u003E\u003Cdiv id=\u0022F1\u0022 class=\u0022fig pos-float  odd\u0022\u003E\u003Cdiv class=\u0022highwire-figure\u0022\u003E\u003Cdiv class=\u0022fig-inline-img-wrapper\u0022\u003E\u003Cdiv class=\u0022fig-inline-img\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/14\/56\/11\/F1.large.jpg?width=800\u0026amp;height=600\u0026amp;carousel=1\u0022 title=\u0022Progression-Free Survival in the BOLERO-1 Entire Study PopulationOne-sided P value is obtained from the log-rank test stratified by prior use of trastuzumab (yes\/no) and visceral metastasis (yes\/no) from Interactive Web Response System.Reproduced with permission from SA Hurvitz, MD.\u0022 class=\u0022fragment-images colorbox-load\u0022 rel=\u0022gallery-fragment-images-1431918335\u0022 data-figure-caption=\u0022\u0026amp;lt;div xmlns=\u0026amp;quot;http:\/\/www.w3.org\/1999\/xhtml\u0026amp;quot;\u0026amp;gt;Progression-Free Survival in the BOLERO-1 Entire Study PopulationOne-sided \u0026amp;lt;em\u0026amp;gt;P\u0026amp;lt;\/em\u0026amp;gt; value is obtained from the log-rank test stratified by prior use of trastuzumab (yes\/no) and visceral metastasis (yes\/no) from Interactive Web Response System.Reproduced with permission from SA Hurvitz, MD.\u0026amp;lt;\/div\u0026amp;gt;\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003E\u003Cimg class=\u0022fragment-image\u0022 alt=\u0022Figure 1.\u0022 src=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/14\/56\/11\/F1.medium.gif\u0022\/\u003E\u003C\/a\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cul class=\u0022highwire-figure-links inline\u0022\u003E\u003Cli class=\u00220 first\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/14\/56\/11\/F1.large.jpg?download=true\u0022 class=\u0022highwire-figure-link highwire-figure-link-download\u0022 title=\u0022Download Figure 1.\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload figure\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00221\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/14\/56\/11\/F1.large.jpg\u0022 class=\u0022highwire-figure-link highwire-figure-link-newtab\u0022 target=\u0022_blank\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EOpen in new tab\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00222 last\u0022\u003E\u003Ca href=\u0022\/highwire\/powerpoint\/11606\u0022 class=\u0022highwire-figure-link highwire-figure-link-ppt\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload powerpoint\u003C\/a\u003E\u003C\/li\u003E\u003C\/ul\u003E\u003C\/div\u003E\u003Cdiv class=\u0022fig-caption\u0022 xmlns:xhtml=\u0022http:\/\/www.w3.org\/1999\/xhtml\u0022\u003E\u003Cspan class=\u0022fig-label\u0022\u003EFigure 1.\u003C\/span\u003E \u003Cp id=\u0022p-7\u0022 class=\u0022first-child\u0022\u003EProgression-Free Survival in the BOLERO-1 Entire Study Population\u003C\/p\u003E\u003Cp id=\u0022p-8\u0022\u003EOne-sided \u003Cem\u003EP\u003C\/em\u003E value is obtained from the log-rank test stratified by prior use of trastuzumab (yes\/no) and visceral metastasis (yes\/no) from Interactive Web Response System.\u003C\/p\u003E\u003Cp id=\u0022p-9\u0022\u003EReproduced with permission from SA Hurvitz, MD.\u003C\/p\u003E\u003Cdiv class=\u0022sb-div caption-clear\u0022\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cp id=\u0022p-10\u0022\u003EPFS was increased with everolimus therapy in the hormone receptor-negative subgroup (20.27 vs 13.08 months; HR, 0.66; log-rank \u003Cem\u003EP\u003C\/em\u003E\u2009=\u2009.0049); however, this did not cross the statistical significance threshold of \u003Cem\u003EP\u2009\u003C\/em\u003E=\u2009.0044 as prespecified in the study protocol, and was therefore considered statistically insignificant.\u003C\/p\u003E\u003Cp id=\u0022p-11\u0022\u003ESimilarly, there was no significant difference in the secondary end points of ORR (\u003Cem\u003EP\u003C\/em\u003E\u2009=\u2009.7276 vs \u003Cem\u003EP\u003C\/em\u003E\u2009=\u2009.4085) and CBR (\u003Cem\u003EP\u003C\/em\u003E\u2009=\u2009.9573 vs \u003Cem\u003EP\u003C\/em\u003E\u2009=\u2009.6382) in the entire study population or the hormone receptor-negative subgroup, respectively.\u003C\/p\u003E\u003Cp id=\u0022p-12\u0022\u003EDr Hurvitz reported increased rates of any-grade stomatitis (67% vs 32%), diarrhea (57% vs 47%), neutropenia (38% vs 25%), and anemia (31% vs 16%) in patients who received everolimus compared with the placebo group. Additionally, on-treatment deaths due to an adverse event (AE) occurred in 3.6% of patients in the everolimus arm, compared with 0 in the placebo arm. All except 1 of these deaths occurred within 15 months of the beginning of the study, she said, adding that this may be associated with a lack of experience in managing the AEs of everolimus in combination with chemotherapy. Careful monitoring and early management of AEs in patients who receive everolimus and chemotherapy is therefore important, she concluded.\u003C\/p\u003E\u003C\/div\u003E\u003Cul class=\u0022copyright-statement\u0022\u003E\u003Cli class=\u0022fn\u0022 id=\u0022copyright-statement-1\u0022\u003E\u00a9 2014 SAGE Publications\u003C\/li\u003E\u003C\/ul\u003E\u003Cspan class=\u0022highwire-journal-article-marker-end\u0022\u003E\u003C\/span\u003E\u003C\/div\u003E\u003Cspan id=\u0022related-urls\u0022\u003E\u003C\/span\u003E\u003C\/div\u003E\u003Ca href=\u0022http:\/\/mdc.sagepub.com\/content\/14\/56\/11.abstract\u0022 class=\u0022hw-link hw-link-article-abstract\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EView Summary\u003C\/a\u003E\u003C\/div\u003E  \u003C\/div\u003E\n\n  \n  \u003C\/div\u003E\n\u003C\/div\u003E\n  \u003C\/div\u003E\n\u003C\/div\u003E\n\u003C\/div\u003E\u003Cscript type=\u0022text\/javascript\u0022 src=\u0022http:\/\/mdc.sagepub.com\/sites\/all\/modules\/highwire\/highwire\/plugins\/highwire_markup_process\/js\/highwire_figures.js?nzm2le\u0022\u003E\u003C\/script\u003E\n\u003Cscript type=\u0022text\/javascript\u0022 src=\u0022http:\/\/mdc.sagepub.com\/sites\/all\/modules\/highwire\/highwire\/plugins\/highwire_markup_process\/js\/highwire_openurl.js?nzm2le\u0022\u003E\u003C\/script\u003E\n\u003C\/body\u003E\u003C\/html\u003E"}