Breaking Research News from sources other than Breastcancer.org
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HER2 Expression on Tumor-Derived Extracellular Vesicles and CTCs
Journal Scan / Research · August 25, 2020
- This study retrospectively reanalyzed stored peripheral blood samples from 114 patients with metastatic HER2-positive breast cancer for the presence of HER2 expression in circulating tumor cells (CTCs) and tumor-derived extracellular vesicles (tdEVs). The inclusion of anti-HER2 targets increased the detection of one CTC in a given sample from 89% to 95%. Interestingly, HER2 was detected in CTCs and tdEVs that express cytokeratin, which is often used to enhance CTC detection. Additionally, a preselected ROC target of 7% HER2+ CK+ tdEVs predicted HER2 expression with 74% sensitivity and specificity when compared with the HER2 amplification status of the primary tumor sample.
- CTC and tdEV heterogeneity in the blood of patients is inversely associated with overall survival.
- These results should be validated with prospective, large-scale analysis of patient samples. However, they present an encouraging prospect for screening for the presence of HER2 based on liquid biopsy.
{Open access}0 -
PBS NewsHour: The Best Health Care? America & the World
The presidential election will determine the course of the U.S. health care system — the most expensive system in the world, brimming with innovation but one that also leaves more than 30 million uninsured. This special series explores how the U.S. health care system stacks up with the rest of the world.
https://www.pbs.org/newshour/series/the-best-healt...
{Video. Free access. 5 segments, each of about 8 to 10 minutes duration.}
Try this 8 question, related quiz: WHAT DOES HEALTH CARE COST AROUND THE WORLD?
https://www.pbs.org/newshour/features/health-cost-...
{It's insightful.}
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Veliparib With Carboplatin and Paclitaxel in BRCA-Mutated Advanced Breast Cancer
- The Lancet Oncology September 03, 2020 This large phase III trial demonstrated that the addition of veliparib (vs placebo) to carboplatin and paclitaxel in more than 500 patients with HER2-negative, germline BRCA mutation–associated breast cancer was well-tolerated and led to improved progression-free survival.Overall survival was similar in the interim analysis, but further follow-up will be needed.
- https://www.practiceupdate.com/C/105768/56?elsca1=...
- https://www.thelancet.com/journals/lanonc/article/...(20)30447-2/fulltext
- DOI:https://doi.org/10.1016/S1470-2045(20)30447-2
- {Press summary which includes MO commentary, free. Registration/log-in may be required; article abstract available free. Full access requires, purchase or subscription.}
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Efficacy of Eribulin for Metastatic Breast Cancer Based on Localization of Specific Secondary Metastases
- Published in Metastatic Breast Cancer September 01, 2020In this post hoc analysis of 1864 pretreated patients with locally advanced/metastatic breast cancer who were treated with eribulin, the authors determined that eribulin was effective independent of metastatic location at baseline. Among patients with bone, lymph node, and chest wall/breast/skin metastases at baseline, there was a small but significant overall survival benefit for patients who received eribulin versus control treatment. Improved overall survival was also observed in patients with liver metastases who received eribulin.These findings suggest that eribulin has benefits for patients with locally advanced or metastatic breast cancer with metastases to bone, liver, lung, lymph node, and chest wall/breast/skin.
{Open access}0 -
Emerging Treatment Strategies for Breast Cancer Brain Metastasis
Published in Metastatic Breast Cancer - August 31, 2020
In this review, the authors discuss currently available clinical treatment options and emerging strategies for patients with breast cancer brain metastases.
Abstract
Systemic therapies for primary breast cancer have made great progress over the past two decades. However, oncologists confront an insidious and particularly difficult problem: in those patients with metastatic breast cancer, up to 50% of human epidermal growth factor 2 (HER2)-positive and 25–40% of triple-negative subtypes, brain metastases (BM) kill most of them. Fortunately, standard- of-care treatments for BM have improved rapidly, with a decline in whole brain radiation therapy and use of fractionated stereotactic radiosurgery as well as targeted therapies and immunotherapies. Meanwhile, advances in fundamental understanding of the basic biological processes of breast cancer BM (BCBM) have led to many novel experimental therapeutic strategies. In this review, we describe the most recent clinical treatment options and emerging experimental therapeutic strategies that have the potential to combat BCBM.
Commentary by Lillie D Shockney RN, BS, MAS, ONN-CG re merits of proactive screening.
https://www.practiceupdate.com/c/104222/67/13/?els...
https://journals.sagepub.com/doi/10.1177/175883592...
https://doi.org/10.1177/1758835920936151
{Open access}
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Targeting HER2 in Breast Cancer Patients With Brain Metastases
- Video Interview with Lee S. Schwartzberg MD, FACP
- Run time 5:12
- Discusses systemic therapy, radiation therapy, and surgical options. Referrencs hippocampal sparing.
- https://www.practiceupdate.com/c/102115/67/13/?els...
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Great news about Eribulin Lumpie. Thanks for posting that. It is in my bucket.
the hard part is reading the median OS numbers.difference in OS was also seen in patients with liver metastases randomized to eribulin versus control (median: 13.4 versus 11.3 months,
😢 2 extra months in overall survival is statistically good but only a median of 13.4 months prolonged OS I guess I should be happy that I am at 17 months and counting and still haven’t achieved PFS
Dee
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While it might not apply to the ER+, HER-, it is comforting that it can beeeee synthetically produced and that stinging not necessary. There was a study about rattlesnake venom a while back, have not heard anything about it recently. Hopefully biting won't be required.
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AlabamaDee : I hear ya! Sometimes it's two steps forward, one step back. Ya think... 2 months? That's all? But 2 months beats 0 months, as long as the QOL is pretty good. Hoping we get some better traction. I don't seem to be having much luck getting to progression free either. Hoping for improvement asap on that front! Hang in htere.
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New Therapy Targets Breast Cancer Metastases In Brain
On Aug 26, 2020
Combination therapy reduces tumor size, dramatically improves survival in mice
CHICAGO — When breast cancer spreads to the brain, the prognosis is grim. Patients only have about six months to live.
Women with HER2-positive breast cancer tend to develop brain metastases in up to 55% of cases. Chemotherapy drugs targeting breast cancer cells in the brain aren't effective, because they can't cross the blood-brain-barrier.
But a new combination therapy targeting breast cancer tumors in the brain dramatically decreased tumor size and increased survival in a study with mice, reports a new Northwestern Medicine study. An estimated 75% of mice that had brain metastases from breast cancer were cured and cancer-free after the therapy.
"The new combination therapy we identified can cross the blood-brain barrier," said lead study author Dr. Maciej Lesniak, Northwestern Medicine chair of neurological surgery and professor of neurosurgery at Northwestern University Feinberg School of Medicine. "The therapy also targets brain metastases and significantly improves survival."
The paper will be published on August 26 in Science Translational Medicine.
The two drugs are tubulin inhibitor, vinorelbine, approved by the U.S. Food and Drug Administration (FDA) and available in clinics, and bromodomain inhibitor, I-BET-762, FDA approved for clinical trials. The bromodomain inhibitor increased βIII-tubulin, a protein found in cancer cells that metastasize to the brain. Overexpression of βIII-tubulin sensitized cancer cells to be killed by vinorelbine.
"The findings of our work set the stage for a clinical trial, whereby patients with breast cancer brain metastases can be treated with the combination of these two drugs," Lesniak said. "This will offer patients with breast cancer brain metastases, who have been systematically excluded from clinical trials, the chance to benefit from a new therapeutic regimen that has been proven to be strongly effective in experimental settings."
Breast cancer spreads to other organs like brain, lung and bone. The metastasis of breast cancer to the brain is a terminal disease and the deadliest complication.
There is a lack of targeted therapies for breast cancer brain metastases, said first study author Deepak Kanojia, research associate in neurological surgery at Feinberg.
"Patients with brain metastases are often excluded from clinical trials due to their poor outcomes and dismal survival," Kanojia said. "Regular systemic therapies, like Herceptin, do not cross the blood-brain-barrier efficiently, and offer no benefit in brain metastases," he said.
How the study worked
Scientists developed a mouse model that can grow multiple brain metastases to simulate what happens in human patients. They injected tumor cells in the intracarotid artery, resulting in the formation of multiple brain tumors. After the tumors grew, scientists treated the mice with the combination therapy. Final results revealed that 75% of the mice that were treated with the combination were cured and cancer-free.
https://scienmag.com/new-therapy-targets-breast-ca...
https://stm.sciencemag.org/content/12/558/eaax2879
DOI: 10.1126/scitranslmed.aax2879
{Open access}
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BlueGirlRedState: I, too, am anti-bite! A few years ago, there were studies about injecting chemo directly into tumors using transcutaneous needle/catheter (much like a biopsy). I gather they were not successful, although I do not know the details. If the bee venom moves toward clinical trials, I will be interested in knowing how they propose to administer it.
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Lumpie, thanks so much for all your work here. I see my MO Tuesday to discuss possibly moving to the Tucatinib, Xeloda, Herceptin combo or maybe a trial for brain mets I love having some knowledge about these things before the follow ups, you all never fail to spread the word and keep up up to date.
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Thanks for your kind words, illimae - and good luck at your follow-up.
My MO + 2nd opinion both pushed Enhertu vs the Tucatinib, Xeloda, Herceptin combo. I think the sequencing is still subject to some debate. I couldn't find any good trials that met my needs this go-round, but I am encouraged that there seems to be some brain mets research going on.
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I wish you the best luck with whatever you decide next and I’ll post any new details about the treatment changes or trial on the brain mets thread after my meeting. Enjoy your weekend 🙂
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Dr. Pegram on the DESTINY-Breast01 Trial With Trastuzumab Deruxtecan in HER2+ Breast Cancer
OncLive - August 27, 2020@{Watch the video at link below. Runtime @ 2:25. Transcript:}
Mark D. Pegram, MD, co-director of Stanford's Molecular Therapeutics Program, and director of the Breast Cancer Oncology Program, at Stanford Women's Cancer Center, discusses the results of the phase 2 DESTINY-Breast01 study examining fam-trastuzumab deruxtecan-nxki (Enhertu; DS-8201) in patients with HER2-positive breast cancer.
Trastuzumab deruxtecan is a HER2 antibody-drug conjugate (ADC) that is based on a backbone sequence of trastuzumab (Herceptin), which is covalently linked to a topoisomerase 1 inhibitor payload exatecan derivative by a tetrapeptide-based cleavable linker, says Pegram. This agent is unique, with many attributions that distinguish it from ado-trastuzumab emtansine (T-DM1; Kadcyla). For example, T-DM1 has about 3.5 molecules per payload per antibody backbone, whereas trastuzumab deruxtecan has a drug-to-antibody ratio of 8, adds Pegram.
The DESTINY-Breast01 study was a 2-part, open-label, single-group, multicenter, phase 2 study. In the first part of the study, 3 doses of trastuzumab deruxtecan were evaluated in order to identify a recommended phase 2 dose, which was determined to be 5.4 mg/kg given intravenously every 3 weeks. In the second part of the study, the efficacy and safety of the recommended dose was documented, says Pegram. Overall, 184 patients were enrolled and they had undergone a median of 6 previous treatments prior to study enrollment.
The overall response rate (ORR) in this heavily pretreated population was 60.9%; this is the highest ORR reported for a single-agent HER2-targeted therapy in such heavily pretreated patients, according to Pegram. The disease control rate was 97.3% at the time of data presentation, adds Pegram. The durability of response with the ADC was also impressive, according to Pegram, with a median progression-free survival (PFS) of 16.4 months.
Moreover, a subset analysis of the trial looked at 24 patients with central nervous system metastasis and showed that the ORR in that subset was approximately 58% with a median PFS of 18.1 months, which is very similar to what had been observed in the intention-to-treat populations. Once the ADC received regulatory approval from the FDA, it became a new practice standard, concludes Pegram.
https://www.onclive.com/view/dr-pegram-on-the-dest...
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Lumpie, picked up your post re brain mets and immediately thought Mae would be keen to see this.....scroll down and there she is! Just know that there’s a whole wee community here who really appreciate you!
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"There was a study about rattlesnake venom a while back, have not heard anything about it recently. Hopefully biting won't be required"
I'm equally terrified and fascinated by Snakes so I've been following this and, no updates.
However, if it takes a bite, I'll sign up 😁
Reality though it won't take a bite, I don't know if it can be synthesized so I wonder (if it actually works) if there's going to be snake milking farms in the future 😃
I do love the fact that people are looking at animals (bees, snakes), our immune system, and recycling other drugs as Cancer treatment. There are so many drugs that have beneficial effects they're not designed for.
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Hi.
I posted my question regarding the following Clinical trial on a vaccine for TNBC, in the TNBC forum, but was also hoping for any input on vaccine clinical trials for any type of BC.
https://clinicaltrials.gov/ct2/show/NCT03012100
I am interested to know about side effects, efficacy, etc. Any input would be appreciated0 -
Karenfizedbo15: Thank you! Made my day!
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New Era for Targeting HER2 Beckons in Breast Cancer and Beyond
OncLive - September 3, 2020
Precision medicine advancements are opening a new chapter in the development of anticancer therapies that target the HER2 pathway, resulting in 3 approvals for breast cancer in less than a year and raising hopes for attacking other cancer types.
In the breast cancer arena, the FDA approved 2 new drugs, fam-trastuzumab deruxtecan-nxki (Enhertu) and tucatinib (Tukysa), and an expanded indication for neratinib (Nerlynx).1-3 Margetuximab, a novel monoclonal antibody (mAb), is hot on their heels, with developer MacroGenics seeking approval following promising phase 3 outcomes.4-6
Efforts to expand HER2-targeted therapy into other HER2-positive cancer types have met with less success over the years. Except for trastuzumab (Herceptin) in gastric cancer,7 there are no approvals outside of breast cancer, and multiple clinical trial failures have underscored that all HER2positive cancers are not created equal.8
Now, however, ongoing clinical trials of novel HER2-targeted therapies in gastric, colorectal (CRC), and non–small cell lung cancers (NSCLCs) are showing promise.9-12
Meanwhile, investigators are exploring the role of HER3, which preferentially partners with HER2 to drive oncogenic signaling in propelling resistance to HER2-targeted therapy.13-15 To date, HER3-targeted mAbs have demonstrated limited clinical efficacy, but the development of a HER2-HER3 bispecific antibody is generating early enthusiasm.16,17
Overall, a variety of approved and novel therapies are in the pipeline for targeting HER2 in a range of tumor types (see Table).
https://www.onclive.com/view/new-era-for-targeting...
{This lengthy article covers a number of interesting topics from new HER2 therapies to targeting HER3 and use of anti-HER2 therapies in the tx of other cancers. THanks for my friend Jackie for the link. Free access.}
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In today's Washington Post (cross posted with are you on a clinical trial):
In a small bottom of the page article in today's Washington Post, it said that AbbVie has struck a deal on a cancer drug with a Chinese drug developer, I-Mab. Abbvie is getting the exclusive global license to develop and sell the Chinese company's cancer-fighting drug known as lemzoparlimab, also known as TJC4, which is an antibody used to treat multiple forms of cancer. According to the article, the drug therapy targets a "do not eat me" signal that allows cancer cells to avoid being targeted by a patient's immune system, blocking the signal to allow the immune system to "engulf and eradicate the malignant cells." Apparently, the Chinese company also has two other antibodies based upon the same drug, and AbbVie will develop those as well.
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Oh interesting BevJen. I was just reading somewhere a brief mention about research on phagocytes being recruited. Sounds like someone has a working phagocyte stimulant with the lemzoparlimab. Phagocytes are some of my favourite cells from when I studied cell biology
I just want these drugs avail quickly on the market!0 -
NorCalS : Many of us hold out hope for vaccines, both as prevention and to stimulate immune response in advanced cancers.
Well, I just wrote a long and detailed response that the page ate. Moral of this story: save your work. I will do what I can to recreate:
Official trial page: NCT03012100
Multi-epitope Folate Receptor Alpha Peptide Vaccine, GM-CSF, and Cyclophosphamide in Treating Patients With Triple Negative Breast Cancer
https://clinicaltrials.gov/ct2/show/NCT03012100
This trial is still recruiting, and I cannot find that it has reported any results yet.
Completion date: July 31, 2021
Required reporting date : July 31, 2022, midnight
Here are a couple of pages that give status reports on the trial. You should also be able to get this on the trial page but sometimes these have a friendlier format:
http://fdaaa.trialstracker.net/trial/NCT03012100/
If you are interested in breast cancer vaccines, I located this table of bc vaccine trials:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6340364/table/t3-bctt-11-053/
Published online 2019 Jan 17. doi: 10.2147/BCTT.S175360
If you are interested in reading about the rationale for breast cancer vaccines, this may be of interest:
Rationale for immunological approaches to breast cancer therapy
https://www.thebreastonline.com/article/S0960-9776(17)30477-0/pdf
DOI:https://doi.org/10.1016/j.breast.2017.06.009
This article references the trial and discusses the rationale for the research:
Folate receptor alpha expression associates with improved disease-free survival in triple negative breast cancer patients
https://www.nature.com/articles/s41523-020-0147-1#citeas
https://doi.org/10.1038/s41523-020-0147-1
Similar here:
Trial Watch: Immunostimulation with recombinant cytokines for cancer therapy
https://www.tandfonline.com/doi/full/10.1080/2162402X.2018.1433982
https://doi.org/10.1080/2162402X.2018.1433982
And here:
Design of an Epitope-Based Vaccine Ensemble for Animal Trypanosomiasis by Computational Methods
https://www.mdpi.com/2076-393X/8/1/130/review_report
https://doi.org/10.3390/vaccines8010130
Here is coverage of the trial in the popular press:
https://www.fox5atlanta.com/news/vaccine-could-prevent-breast-ovarian-lung-cancer
I believe that all references cited allow free access. This should be enough to keep any of us reading for a while! Bon chance!
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Here is a link to the WaPo article BevJen referenced above:
AbbVie strikes deal on Chinese cancer treatment drug that may be worth $2.9 billion
https://www.washingtonpost.com/business/economy/ab...
The article calls the drug lemzoparlimab and TJC4 but neither of those comes up when I search the clinical trials.gov database.
Here is the Abbvie press release on the deal:
https://news.abbvie.com/news/press-releases/abbvie...
Also, the OncLive article posted above,
New Era for Targeting HER2 Beckons in Breast Cancer and Beyond
OncLive - September 3, 2020
discusses a drug "conditionally approved in China" but it seems to be a different drug, Pyrotinib. Here is the trial cited: "Results of a planned interim analysis of the phase 3 PHOEBE trial (NCT03080805) in patients with previously treated HER2positive MBC were presented at 2020 ASCO." Two other trials are referenced: Poziotinib (16 mg/day orally) produced an ORR of 42% in the first 12 evaluable patients in its trial (NCT03066206). For pyrotinib (400 mg daily), the ORR was 31.7% among 60 patients (NCT02834936). Both drugs had an acceptable safety profile."
Well, there are lots of companies excited to sell us thier drugs. I hope some of them work.
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Lumpie,
Thanks again for the information. I will review and ask MO to help me get into a vaccine clinical trial
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Thought I would share
https://clinicaltrials.gov/ct2/show/NCT04288089?term=04288089&draw=2&rank=1#contactlocationH3B-6545 represents a new class of ERα antagonists discovered by H3 Biomedicine scientists called "Selective Estrogen Receptor Covalent Antagonists" (SERCAs). SERCAs inactivate the estrogen receptor by targeting a cysteine that is not present in the majority of other nuclear hormone receptors. SERCAs have a unique biological activity profile compared to Selective Estrogen Receptor Modulators (SERMs) and Selective Estrogen Receptor Degraders (SERDs).https://www.h3biomedicine.com/2017/09/05/h3-biomedicine-announces-first-patient-dosed-with-h3b-6545-in-phase-1-study-in-breast-cancer/
This article says stable and partial response-https://ascopubs.org/doi/abs/10.1200/JCO.2019.37.15_suppl.1059
Dee0 -
found another one
OP-1250 is a small molecule Complete Estrogen Receptor ANtagonist (CERAN). OP-1250 potently competes with the endogenous activating estrogenic ligand 17-beta estradiol for binding in the ligand binding pocket. OP-1250 blocks estrogen-driven transcriptional activity, inhibits estrogen-driven breast cancer cell growth, and induces degradation of the estrogen
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Dear All, Daiichi Sankyo is about to end another ADC's (Patritumab Deruxtecan, U3-1402) Ph2 clinical trial. It is an interesting ADC that targets HER3 and has to be as effective as DS-8201. Let's keep an eye on that one. Actually I found an interesting link where if you scroll down a bit, you can find a database of all developed ADCs and by using filter "Breast Cancer", you can get all of them related to BC. Just go through them, there are many links to clinical trials in everyone of them: https://www.adcreview.com/drugmap/u3-1402-patritum...
Saulius
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Targeting Breast Cancer Cells and Leaving Healthy Cells Unscathed
...Now scientists at Johns Hopkins Medicine and the University of Oxford say they have found a new way to kill multiplying human breast cancer cells by selectively attacking the core of their cell division machinery. The method, only tested on lab-grown and patient-derived cancer cells, could advance efforts to find drugs that kill breast cancer cells in a subset of patients...
The research team looked for cell division mechanisms specific to cancer cells in a variety of lab-grown cells. During their search, they encountered a line of human breast cancer cells that are very dependent on cell structures called centrioles to divide and survive....
Further observations revealed that the centriole-dependent breast cancer cells had a section of genome that had been abnormally copied many times, an alteration found in about 9% of breast cancers. The researchers observed the genes encoded in the highly copied region and found a gene that was producing high levels of a protein called TRIM37 shown to control centrosomes...
They used a PLK4 inhibitor known to disrupt proteins that make centrioles, which interfered with TRIM37. When they added the drug to the lab-grown cancer cells with normal TRIM37 levels, they found that the cells were able to divide, even though the drug had removed the cell's centrioles. When the drug was added to breast cancer cells with high TRIM37 levels the cells were not able to divide and most cells stopped growing or died.
"The idea would be to identify tumors with high levels of TRIM37 and use a PLK4 inhibitor to selectively kill cancer cells and leave healthy cells relatively unharmed," explained Holland.
https://www.genengnews.com/news/targeting-breast-c...
paper: https://www.nature.com/articles/s41586-020-2690-1....
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Combining nanotechnology and immunotherapy to fight MBC.
https://medicalxpress.com/news/2020-09-breast-cancer-nanotech-immunotherapy.html
“Efstathios "Stathis" Karathanasis, an associate professor of biomedical engineering, is directing the novel technique—sending nanoparticles into the body to wake up "cold" tumors so they can be located and neutralized by immune cells. The team also includes researchers from Cleveland Clinic and Duke University.““The NCI recently awarded a five-year, $3 million grant to Karathanasis and his team to continue their research, initially on animal models with an eye toward human trials. Much of the groundwork behind the project is described in a paper published in Cancer Research, the official journal of the American Association for Cancer Research.
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