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YSC Research Updates
Posted By Michelle Esser, Program Manager, Advocacy and Research On April 9, 2014 @ 10:00 am In Guest Bloggers,The Business of Breast Cancer,YSC SYNC - Survivors | No Comments
YSC wants to keep our constituents updated on relevant medical news, and we have three breast cancer updates to share. They include: (1) FDA approval of Perjeta before surgery in HER2+ breast cancer; (2) the PALOMA study that includes young women in the study of a new drug for women with hormone receptor positive metastatic breast cancer; and (3) the BROCADE study which will also enroll young women with a BRCA mutation to test veliparib, a PARP inhibitor, in women with recurrent or metastatic breast cancer.
This past fall, the FDA granted accelerated approval of the drug Perjeta (Pertuzumab) for use before surgery (also called “neoadjuvant” use) in women with HER2+ early stage breast cancer. The FDA approval was based on the NEOSPHERE (Neoadjuvant Study of Pertuzumab and Herceptin in an Early Regimen Evaluation) study which showed that four cycles (12 weeks) of treatment with Perjeta, Herceptin and Docetaxel (Taxotere) in patients with HER2+, locally advanced inflammatory or early stage breast cancer, significantly improved the rate of total pathological complete response (pCR) prior to surgery. A total pCR occurs when, at the time of surgery, there is no detectable evidence of breast cancer remaining. In the Perjeta, Herceptin, and Docetaxel group, 39.3% of patients experienced a pCR, compared to 21.5% in the group without Perjeta (receiving Herceptin and Docetaxel only). The most common side effects from Perjeta include a reduction in white blood cell counts, diarrhea, and hair loss, although heart problems are a potential serious side effect which should be closely monitored.
Like Herceptin, Perjeta targets the HER2 receptor, a protein found in large quantities on the outside of HER2+ cancer cells. Perjeta works nicely with Herceptin as they both bind to different places and may result in a greater blocking of the HER signaling pathway and therefore slow the growth of or kill the cancer cells. Perjeta was previously approved by the FDA for use in women with metastatic HER2+ breast cancer who had not yet received anti-HER2 therapy or chemotherapy for metastatic breast cancer.
Perjeta is the first treatment specifically approved by the FDA for neoadjuvant use and marks the first time that FDA granted a drug approval based upon pCR. The FDA’s accelerated approval mechanism  is a conditional approval, which makes it possible for drugs shown in early studies to have a clinical benefit to be available to patients more quickly, with full FDA approval granted later if additional studies confirm the drug’s benefit and safety. The FDA will examine results from the ongoing APHINITY trial (examining chemotherapy and Herceptin with and without Perjeta), expected to be completed in 2016, to determine whether a full approval will be given to Perjeta. There is currently no data which shows whether Perjeta prior to surgery improves overall survival.
Two Studies for Metastatic Breast Cancer to Include Young Women
Young women are not always included in clinical trials, especially in the metastatic setting, so we want to be sure that you are aware of two current offerings.
PALOMA-3 is a Pfizer-sponsored Phase 3 trial to investigate its drug palbociclib in women with hormone receptor positive (HR+), HER2 negative, metastatic breast cancer whose disease has progressed after prior endocrine (hormonal) therapy. Palbociclib blocks cyclin-dependent kinases 4 and 6 (proteins upregulated in many tumor cell types that regulate cell replication), thereby hindering tumor cell progression. An interim analysis of a Phase 2 trial of palbociclib, presented at San Antonio Breast Cancer Symposium in 2012, showed progression-free survival (period of time without tumor progression) of 26.1 months for patients on palbociclib plus an aromatase inhibitor letrozole (Femara) compared to 7.5 months for patients on letrozole alone. This same study showed that neutropenia, a low number of neutrophils (type of white blood cell), was the most common side effect.
Two phase 3 trials of palbociclib are now enrolling for women with metastatic breast cancer that is HR+, HER2 negative and that progressed after prior endocrine therapy. One trial is for post-menopausal women and the other includes pre and peri-menopausal women ages 18 and older. Pre and perimenopausal women will be given an LHRH antagonist shot to shut down the ovaries. In this double blind, placebo-controlled trial, patients will be randomized to receive either palbociclib and fulvestrant (an estrogen receptor antagonist also known as Faslodex, used after a patient’s tumor has progressed on other antiestrogen therapy) or a placebo and fulvestrant. The researchers will examine whether the addition of palbociclib prolongs progression-free survival and compare safety between the two arms. Palbociclib is an oral medication dosed daily for 3 weeks with one week off while fulvestrant is a shot administered at regular intervals. For more details on this trial, please visit:
A new international clinical trial is enrolling patients of all ages with metastatic or recurrent breast cancer who are BRCA 1 or 2 positive to test the efficacy and safety of veliparib, a PARP (poly ADP-ribose polymerase) inhibitor to be used in conjunction with chemotherapy. A PARP inhibitor is a targeted therapy which interferes with a cancer cell’s ability to repair DNA and may lead to death of cancer cells. Because it is a “targeted” therapy, the drug goes after only the cancer-related cells rather than all cells. PARP inhibitors have shown mixed results in prior studies, but it is believed that they hold promise in breast cancers with BRCA 1/2 mutations.
Participants in BROCADE will be randomized to one of three treatment arms: (1) Veliparib with temozolomide (Temodar) (an oral chemotherapy); (2) Veliparib with carboplatin and paclitaxel (both regimens given through infusion, the latter known as Taxol); or (3) placebo with carboplatin and paclitaxel. Common side effects of PARP inhibitors include anemia, fatigue, nausea and vomiting. More than two prior cancer treatments for metastatic breast cancer and/or a prior taxane therapy for metastatic breast cancer as well as brain metastases may exclude study participation. This study is being conducted by AbbVie, formerly part of Abbott Laboratories. For more details on this study, please visit: http://www.clinicaltrials.gov/ct2/show/NCT01506609?term=veliparib&rank=3 
This information is presented for educational purposes only. These treatments may not be available or best for everyone. As always, please consult your physician for details on the best treatments for you.
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URLs in this post:
 accelerated approval mechanism: http://www.fda.gov/forconsumers/byaudience/forpatientadvocates/speedingaccesstoimportantnewtherapies/ucm128291.htm
 http://clinicaltrials.gov/ct2/show/NCT01942135?term=PALOMA&rank=1: http://clinicaltrials.gov/ct2/show/NCT01942135?term=PALOMA&rank=1
 http://www.clinicaltrials.gov/ct2/show/NCT01506609?term=veliparib&rank=3: http://www.clinicaltrials.gov/ct2/show/NCT01506609?term=veliparib&rank=3
 http://www.gene.com/media/press-releases/14548/2013-09-30/fda-grants-genentechs-perjeta-accelerate: http://www.gene.com/media/press-releases/14548/2013-09-30/fda-grants-genentechs-perjeta-accelerate
 http://www.genomeweb.com/clinical-genomics/asco-pfizer-unveils-study-er-positive-her2-negative-breast-cancer-rx-herceptin-b: http://www.genomeweb.com/clinical-genomics/asco-pfizer-unveils-study-er-positive-her2-negative-breast-cancer-rx-herceptin-b
 http://cdmrp.army.mil/bcrp/research_highlights/13slamon_highlight.shtml: http://cdmrp.army.mil/bcrp/research_highlights/13slamon_highlight.shtml
 www.BROCADEStudy.com: http://www.BROCADEStudy.com
 http://annonc.oxfordjournals.org/content/early/2010/07/19/annonc.mdq322.full: http://annonc.oxfordjournals.org/content/early/2010/07/19/annonc.mdq322.full
 http://www.onclive.com/publications/oncology-live/2012/july-2012/the-parp-inhibitors-down-but-not-out/2: http://www.onclive.com/publications/oncology-live/2012/july-2012/the-parp-inhibitors-down-but-not-out/2
 http://www.facingourrisk.org/information_research/newsletter_archives/2013spring/parp-inhibitor-research.php: http://www.facingourrisk.org/information_research/newsletter_archives/2013spring/parp-inhibitor-research.php
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