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Topic: Breaking Research News from sources other than breastcancer.org

Forum: Clinical Trials, Research News, Podcasts, and Study Results —

Share your research articles, interpretations and experiences here. Let us know how these studies affect you and your decisions.

Posted on: Nov 21, 2017 05:31AM - edited Nov 21, 2017 05:35AM by Lumpie

Lumpie wrote:

I watch for research news on breast cancer, treatments, etc., and frequently see interesting articles. There is a topic on BCO called "Breaking Research News from Breastcancer.org." One of the moderators suggested that another topic might be appropriate for posting links and synopses of reports on research found elsewhere. So here it is! Please post links to reports on research form reliable sources. Thanks for sharing!

"We must be willing to let go of the life we have planned, so as to have the life that is waiting for us." "If adventures will not befall a young lady in her own village, she must seek them abroad." "Buy the ticket, take the ride." Dx 2015, DCIS/IDC, Right, 3cm, Stage IIA, Grade 3, 0/1 nodes, ER-/PR-, HER2+ (IHC) Chemotherapy 1/14/2016 Cytoxan (cyclophosphamide), Taxotere (docetaxel) Targeted Therapy 1/14/2016 Herceptin (trastuzumab) Dx 2017, IDC, Stage IV, metastasized to liver, ER-/PR-, HER2+ Surgery Lumpectomy: Right Surgery Lumpectomy: Right Radiation Therapy Whole-breast: Breast
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Jul 5, 2020 11:32PM Lumpie wrote:

Efficacy and Safety of T-DM1 + Capecitabine vs T-DM1 Alone in Previously Treated ERBB2+ Metastatic Breast Cancer
JAMA Oncology

  • The authors of this phase I/II randomized clinical trial of 161 patients with previously treated ERBB2-positive metastatic breast cancer compared trastuzumab emtansine (T-DM1) with T-DM1 plus capecitabine. The overall response rate was numerically higher with combination therapy (44% vs 36%; P = .34). The median progression-free survival was similar between groups. Toxicity was higher with the addition of capecitabine, and more patients discontinued treatment due to adverse events in the combination arm compared with the T-DM1 monotherapy arm.
  • Chemotherapy adds only modest potential benefit to T-DM1 while increasing toxicity.

https://www.practiceupdate.com/C/102841/56

https://pubmed.ncbi.nlm.nih.gov/32584367/

"We must be willing to let go of the life we have planned, so as to have the life that is waiting for us." "If adventures will not befall a young lady in her own village, she must seek them abroad." "Buy the ticket, take the ride." Dx 2015, DCIS/IDC, Right, 3cm, Stage IIA, Grade 3, 0/1 nodes, ER-/PR-, HER2+ (IHC) Chemotherapy 1/14/2016 Cytoxan (cyclophosphamide), Taxotere (docetaxel) Targeted Therapy 1/14/2016 Herceptin (trastuzumab) Dx 2017, IDC, Stage IV, metastasized to liver, ER-/PR-, HER2+ Surgery Lumpectomy: Right Surgery Lumpectomy: Right Radiation Therapy Whole-breast: Breast
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Jul 6, 2020 08:04PM Lumpie wrote:

FDA OKs Bavencio as first-line bladder cancer therapy

Bavencio, or avelumab, Pfizer and Merck's immunotherapy, was approved by the FDA as a maintenance treatment for patients who have locally advanced or metastatic bladder cancer whose disease didn't progress after undergoing first-line platinum-containing chemotherapy.

Avelumab is already approved in bladder cancer patients whose disease has progressed following chemotherapy. Bavencio has been approved for maintenance treatment of patients with locally advanced or metastatic urothelial carcinoma that has not progressed with first-line platinum containing chemotherapy. Avelumab is indicated for the treatment of metastatic Merkel cell carcinoma (MCC).

BAVENCIO® (avelumab) is the FIRST and ONLY FDA-approved human anti-PD-L1 immunotherapy with DUAL ENGAGEMENT of both the adaptive and innate immune systems. BAVENCIO has been shown to release the suppression of the T cell-mediated antitumor immune response by blocking the interaction of PD-L1 with PD-1 receptors in preclinical models. BAVENCIO has also been shown to induce NK cell-mediated direct tumor cell lysis via antibody-dependent cell-mediated cytotoxicity (ADCC) in vitro.

https://pharmaphorum.com/news/fda-approves-pfizer-merck-kgaas-bavencio-in-first-line-bladder-cancer/

{Avelumab is currently being studied as a therapy for HER2+ MBC in the Aviator clinical trial.}

https://clinicaltrials.gov/ct2/show/NCT03414658

"We must be willing to let go of the life we have planned, so as to have the life that is waiting for us." "If adventures will not befall a young lady in her own village, she must seek them abroad." "Buy the ticket, take the ride." Dx 2015, DCIS/IDC, Right, 3cm, Stage IIA, Grade 3, 0/1 nodes, ER-/PR-, HER2+ (IHC) Chemotherapy 1/14/2016 Cytoxan (cyclophosphamide), Taxotere (docetaxel) Targeted Therapy 1/14/2016 Herceptin (trastuzumab) Dx 2017, IDC, Stage IV, metastasized to liver, ER-/PR-, HER2+ Surgery Lumpectomy: Right Surgery Lumpectomy: Right Radiation Therapy Whole-breast: Breast
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Jul 8, 2020 09:04PM Lumpie wrote:

Efficacy and Safety of T-DM1 + Capecitabine vs T-DM1 Alone in Previously Treated ERBB2+ Metastatic Breast Cancer
  • The authors of this phase I/II randomized clinical trial of 161 patients with previously treated ERBB2-positive metastatic breast cancer compared trastuzumab emtansine (T-DM1) with T-DM1 plus capecitabine. The overall response rate was numerically higher with combination therapy (44% vs 36%; P = .34). The median progression-free survival was similar between groups. Toxicity was higher with the addition of capecitabine, and more patients discontinued treatment due to adverse events in the combination arm compared with the T-DM1 monotherapy arm.
  • Chemotherapy adds only modest potential benefit to T-DM1 while increasing toxicity.
  • Adding capecitabine to T-DM1 did not statistically increase ORR associated with T-DM1 in patients with previously treated ERBB2-positive mBC. The combination group reported more AEs, but with no unexpected toxic effects.
https://www.practiceupdate.com/C/102841/56?elsca1=emc_enews_topic-alert
https://jamanetwork.com/journals/jamaoncology/fullarticle/2767391
doi:10.1001/jamaoncol.2020.1796
{For the sake of clarity, it seems that HER2+ breast cancer is now being called ERBB2-positive breast cancer. I think it is a more specific reference to the mutation that causes the problem (uncontrolled growth) but I haven't seem a concise explanation for the change in practice.}
"We must be willing to let go of the life we have planned, so as to have the life that is waiting for us." "If adventures will not befall a young lady in her own village, she must seek them abroad." "Buy the ticket, take the ride." Dx 2015, DCIS/IDC, Right, 3cm, Stage IIA, Grade 3, 0/1 nodes, ER-/PR-, HER2+ (IHC) Chemotherapy 1/14/2016 Cytoxan (cyclophosphamide), Taxotere (docetaxel) Targeted Therapy 1/14/2016 Herceptin (trastuzumab) Dx 2017, IDC, Stage IV, metastasized to liver, ER-/PR-, HER2+ Surgery Lumpectomy: Right Surgery Lumpectomy: Right Radiation Therapy Whole-breast: Breast
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Jul 9, 2020 07:51PM Lumpie wrote:

EMA speeds review of AZ, Daiichi Sankyo HER2 drug Enhertu

The European Medicines Agency will fast-track its review of AstraZeneca and Daiichi Sankyo's HER2-positive breast cancer candidate Enhertu, or trastuzumab deruxtecan. The FDA approved the antibody drug conjugate as a treatment for metastatic HER2-positive disease in December.

http://www.pmlive.com/pharma_news/ema_fast-tracks_review_of_azdaiichi_sankyos_her2_drug_1344455


"We must be willing to let go of the life we have planned, so as to have the life that is waiting for us." "If adventures will not befall a young lady in her own village, she must seek them abroad." "Buy the ticket, take the ride." Dx 2015, DCIS/IDC, Right, 3cm, Stage IIA, Grade 3, 0/1 nodes, ER-/PR-, HER2+ (IHC) Chemotherapy 1/14/2016 Cytoxan (cyclophosphamide), Taxotere (docetaxel) Targeted Therapy 1/14/2016 Herceptin (trastuzumab) Dx 2017, IDC, Stage IV, metastasized to liver, ER-/PR-, HER2+ Surgery Lumpectomy: Right Surgery Lumpectomy: Right Radiation Therapy Whole-breast: Breast
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Jul 10, 2020 08:23AM BSandra wrote:

Wow Lumpie, that is very good news... I think a drug with such profile, if approved in EU, would be compensated in my country pretty soon (I mean in a year/few years). Hopefully... Saulius

Since Dec 2019: NED. Feb 2019: local recurrence in left breast, IBC. May 2018-Feb 2019: NED. Jun 2018: Omega3:Omega6, Cp lowering, CBD/CBDA, DC/CIK. Aug 2017: stage IV de novo at age 33. Dx 8/4/2017, IDC, Left, 6cm+, Stage IV, metastasized to liver, Grade 2, ER-/PR-, HER2+ (IHC) Chemotherapy 8/27/2017 Taxotere (docetaxel) Targeted Therapy 8/28/2017 Herceptin (trastuzumab) Targeted Therapy 8/28/2017 Perjeta (pertuzumab) Chemotherapy 3/12/2019 Taxotere (docetaxel) Surgery 7/22/2019 Mastectomy: Left Radiation Therapy 9/9/2019 Whole-breast: Lymph nodes, Chest wall
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Jul 10, 2020 02:37PM AlabamaDee wrote:

just got this in my email

https://www.practiceupdate.com/content/prognostic-value-of-modified-ihc4-score-in-patients-with-er-metastatic-breast-cancer/102320

so I wasn’t aware of an immunohistochemical prognostic model score. Now there is a modified mICH4 that can possibly help doctors know if they should give hormone therapy or chemotherapy first.

Can anyone shed some light on this?

Dee

Primary neuroendocrine breast cancer Dx 5/23/2013, Right, 1cm, Stage IIB, Grade 2, 1/22 nodes, ER+/PR+, HER2- (FISH) Chemotherapy 7/29/2013 Cytoxan (cyclophosphamide), Taxotere (docetaxel) Dx 4/2019, Stage IV, metastasized to liver, ER+/PR+, HER2- Chemotherapy Doxil (doxorubicin) Targeted Therapy Afinitor (everolimus) Hormonal Therapy Faslodex (fulvestrant) Hormonal Therapy Arimidex (anastrozole), Aromasin (exemestane), Fareston (toremifene), Femara (letrozole) Hormonal Therapy Faslodex (fulvestrant) Targeted Therapy Verzenio Chemotherapy Xeloda (capecitabine)
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Jul 10, 2020 11:34PM Lumpie wrote:

Acquired ESR1 Mutations Predict Poor Benefit from Further AI Therapy in Metastatic Breast Cancer

Patients with hormone receptor (HR) positive metastatic breast cancer who acquired ESR1 mutations during prior aromatase inhibitor therapy had worse survival when treated with the aromatase inhibitor exemestane compared with fulvestrant, a combined analysis of the phase 3 SoFEA and EFECT trials found. The results were recently reported in Clinical Cancer Research.

https://www.cancertherapyadvisor.com/home/cancer-topics/breast-cancer/esr1-mutations-acquired-breast-predict-poor-benefit-further-ai-therapy/?utm_source=newsletter&utm_medium=email&utm_campaign=cta-update-hay-20200710&cpn=&hmSubId=nIej-0ANyLQ1&hmEmail=02k_9hvA1kiS6nmG9LnGT5WH-O6RhZf90&NID=&email_hash=f6f19b3bf12938acdd2c69cb86958025&dl=0&mpweb=1323-98397-6515878

https://clinicaltrials.gov/ct2/show/NCT00065325

https://www.clinicaltrials.gov/ct2/show/NCT00253422

Turner NC, Swift C, Kilburn LS, et al. ESR1 mutations and overall survival on fulvestrant versus exemestane in advanced hormone receptor positive breast cancer: A combined analysis of the phase III SoFEA and EFECT trial [published online June 16, 2020]. Clin Cancer Res. doi: 10.1158/1078-0432.CCR-20-0224

"We must be willing to let go of the life we have planned, so as to have the life that is waiting for us." "If adventures will not befall a young lady in her own village, she must seek them abroad." "Buy the ticket, take the ride." Dx 2015, DCIS/IDC, Right, 3cm, Stage IIA, Grade 3, 0/1 nodes, ER-/PR-, HER2+ (IHC) Chemotherapy 1/14/2016 Cytoxan (cyclophosphamide), Taxotere (docetaxel) Targeted Therapy 1/14/2016 Herceptin (trastuzumab) Dx 2017, IDC, Stage IV, metastasized to liver, ER-/PR-, HER2+ Surgery Lumpectomy: Right Surgery Lumpectomy: Right Radiation Therapy Whole-breast: Breast
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Jul 11, 2020 11:15AM JoynerL wrote:

Thanks, Lumpie. This is such good information. I'm glad we have so many eyes scouring the news.

--Lynn Dx 12/1990, IDC, Left, <1cm, Stage IIA, ER+ Surgery 1/2/1991 Lymph node removal: Underarm/Axillary; Mastectomy: Left; Reconstruction (left): Nipple reconstruction, Saline implant Chemotherapy 1/15/1991 CMF Hormonal Therapy 6/30/1991 Tamoxifen pills (Nolvadex, Apo-Tamox, Tamofen, Tamone) Hormonal Therapy 10/31/2002 Evista (raloxifene) Dx 2/9/2017, IDC, Left, 1cm, Stage IV, metastasized to bone, ER+/PR-, HER2- Hormonal Therapy 3/5/2017 Faslodex (fulvestrant) Targeted Therapy 3/5/2017 Ibrance (palbociclib) Chemotherapy 1/17/2019 Xeloda (capecitabine) Targeted Therapy
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Jul 13, 2020 06:36PM Hopeful82014 wrote:

BMI-Related Differential Benefit of Adjuvant Docetaxel in Early Breast Cancer

Journal of Clinical Oncology



TAKE-HOME MESSAGE
This retrospective analysis evaluated the impact of body mass index
(BMI) in patients with breast cancer treated with docetaxel-based versus
non–docetaxel based chemotherapy in a large adjuvant therapy trial.

A higher BMI was associated with worse disease-free survival and
overall survival among docetaxel-treated patients. No difference was
seen in the non–docetaxel treated patients. These findings of a
differential response to docetaxel according to BMI require validation
in an independent cohort.

– Paul J. Hampel, MD





https://www.practiceupdate.com/content/bmi-related...


Dx IDC
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Jul 13, 2020 08:46PM Lumpie wrote:

ASCO develops guideline for management of men with breast cancer

Research has led to major improvements in breast cancer diagnosis, treatment and survival. However, men with breast cancer represent only 1% of the U.S. breast cancer population and have not been emphasized in this research.

"Nearly all clinical trial participants have been women," Michael J. Hassett, MD, MPH, medical oncologist at Dana-Farber Cancer Institute and lead author of ASCO's guideline on management of male breast cancer, said in an interview with Healio. "When so few men have been included in the trials, it's hard to draw conclusions about how to treat men vs. women. Considering that more than 95% of breast cancers in men are hormone receptor positive, some have suggested that men and women with breast cancer should be treated differently."

https://www.healio.com/news/hematology-oncology/20200708/asco-develops-guideline-for-management-of-men-with-breast-cancer?utm_source=selligent&utm_medium=email&utm_campaign=news&m_bt=6155829948217


"We must be willing to let go of the life we have planned, so as to have the life that is waiting for us." "If adventures will not befall a young lady in her own village, she must seek them abroad." "Buy the ticket, take the ride." Dx 2015, DCIS/IDC, Right, 3cm, Stage IIA, Grade 3, 0/1 nodes, ER-/PR-, HER2+ (IHC) Chemotherapy 1/14/2016 Cytoxan (cyclophosphamide), Taxotere (docetaxel) Targeted Therapy 1/14/2016 Herceptin (trastuzumab) Dx 2017, IDC, Stage IV, metastasized to liver, ER-/PR-, HER2+ Surgery Lumpectomy: Right Surgery Lumpectomy: Right Radiation Therapy Whole-breast: Breast
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Jul 13, 2020 08:53PM Lumpie wrote:

Many negative trials presented with 'not-negative conclusions' at oncology meetings

Increased attention should be paid to the conclusions of formally negative trials discussed during oral presentations at oncology meetings, as many convey a not-negative message, according to a research letter published in JAMA Oncology.

"During [the 2019] ASCO Annual Meeting, several trials presented were considered formally negative according to their primary analysis, but they were presented with ambiguous and not-negative conclusions," Massimo Di Maio, MD, researcher in the department of oncology at University of Turin in Torino, Italy, told Healio. "My colleagues and I later decided to perform a systemic review to better understand the real magnitude of this phenomenon. We started with ASCO 2019, but later found that the proportion of those clinical trials was not negligible. We then extended the analysis to the [European Society for Medical Oncology] meeting, covering 3 years in total."

"Our aim was to be provocative," Di Maio said. "We do not want to be considered fundamentalists of clinical research methodology, because we ... know that even in a formally negative trial there could be many potentially important findings and many ideas for further research.

"...It would be interesting to compare the conclusions included in the oral presentation of these trials with the conclusions of their final publication in a peer-reviewed journal. It was too early to perform this analysis when we wrote this letter, but this could be an interesting follow-up."

https://www.healio.com/news/hematology-oncology/20200710/many-negative-trials-presented-with-notnegative-conclusions-at-oncology-meetings?utm_source=selligent&utm_medium=email&utm_campaign=news&m_bt=6155829948217

"We must be willing to let go of the life we have planned, so as to have the life that is waiting for us." "If adventures will not befall a young lady in her own village, she must seek them abroad." "Buy the ticket, take the ride." Dx 2015, DCIS/IDC, Right, 3cm, Stage IIA, Grade 3, 0/1 nodes, ER-/PR-, HER2+ (IHC) Chemotherapy 1/14/2016 Cytoxan (cyclophosphamide), Taxotere (docetaxel) Targeted Therapy 1/14/2016 Herceptin (trastuzumab) Dx 2017, IDC, Stage IV, metastasized to liver, ER-/PR-, HER2+ Surgery Lumpectomy: Right Surgery Lumpectomy: Right Radiation Therapy Whole-breast: Breast
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Jul 14, 2020 08:24PM Lumpie wrote:

A novel HER2-targeted antibody-drug conjugate offers the possibility of clinical dosing at trastuzumab-equivalent exposure levels

Molecular Cancer Therapeutics

Trastuzumab and the related antibody-drug conjugate (ADC), ado-trastuzumab emtansine (T-DM1), both target HER2-overexpressing cells. Together, these drugs have treatment indications in both early-stage and metastatic settings for HER2+ breast cancer. T-DM1 retains the antibody functionalities of trastuzumab and adds the potency of a cytotoxic maytansine payload. Interestingly, in the clinic, T-DM1 cannot always replace the use of trastuzumab plus chemotherapy administered together as single agents. We hypothesize that this failure may be due in part to the limited systemic exposure achieved by T-DM1 relative to trastuzumab because of toxicity-related dosing constraints on the ADC. We have developed a trastuzumab-based ADC site-specifically conjugated to maytansine through a noncleavable linker. This construct, termed CAT-01-106, has a drug-to-antibody ratio (DAR) of 1.8, approximately half the average DAR of T-DM1, which comprises a mixture of antibodies variously conjugated with DARs ranging from 0-8. The high DAR species present in T-DM1 contribute to its toxicity and limit its clinical dose. CAT-01-106 showed superior in vivo efficacy compared to T-DM1 at equal payload dosing and was equally or better tolerated compared to T-DM1 at equal payload dosing up to 120 mg/kg in Sprague-Dawley rats and 60 mg/kg in cynomolgus monkeys. CAT-01-106 also showed improved pharmacokinetics in rats relative to T-DM1, with 40% higher ADC exposure levels. Together, the data suggest that CAT-01-106 may be sufficiently tolerable to enable clinical dosing at trastuzumab-equivalent exposure levels, combining the functions of both the antibody and the payload in one drug and potentially improving patient outcomes.

https://www.meta.org/papers/a-novel-her2targeted-a...

DOI: 10.1158/1535-7163.mct-20-0190


"We must be willing to let go of the life we have planned, so as to have the life that is waiting for us." "If adventures will not befall a young lady in her own village, she must seek them abroad." "Buy the ticket, take the ride." Dx 2015, DCIS/IDC, Right, 3cm, Stage IIA, Grade 3, 0/1 nodes, ER-/PR-, HER2+ (IHC) Chemotherapy 1/14/2016 Cytoxan (cyclophosphamide), Taxotere (docetaxel) Targeted Therapy 1/14/2016 Herceptin (trastuzumab) Dx 2017, IDC, Stage IV, metastasized to liver, ER-/PR-, HER2+ Surgery Lumpectomy: Right Surgery Lumpectomy: Right Radiation Therapy Whole-breast: Breast
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Jul 15, 2020 04:01AM debbew wrote:

[Tests in mice show] New therapy extends breast cancer survival rate, prevents reoccurrence

A new immunotherapy developed by researchers at Northwestern University dramatically extends the survival time of mice with triple negative breast cancer, one of the most aggressive and difficult-to-treat forms of breast cancer.

In a new study, mice treated with the therapy, which comprises two immunity-boosting drugs housed inside a nanoparticle, experienced complete tumor remission for at least 100 days. All untreated mice died by day 30. None of the treated mice experienced adverse side effects or autoimmune responses...

The research will be published online this week in the Proceedings of the National Academy of Sciences...

"It's definitely prolonging survival," Callmann noted. "Even if not all mice were completely cured."

Mirkin and his team also found that the SNA-based immunotherapy protected the mice from relapsing. After the mice entered remission, the team attempted to reimplant the mice with cancer, but tumors did not grow...

The researchers believe that, in theory, SNA-based immunotherapies should be an effective treatment for many types of cancer. Mirkin's team plans to explore that next. Mirkin notes that he feels encouraged that four SNA drugs are already in human clinical trials, including a variant of the SNA used in this study in a type of immunotherapy for Merkel Cell carcinoma. That structure also was invented at Northwestern and is in a Phase 2 clinical trial conducted by Exicure, a clinical stage biotechnology startup.

https://news.northwestern.edu/stories/2020/07/new-therapy-extends-breast-cancer-survival-rate-prevents-reoccurrence/

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Jul 15, 2020 05:18AM Lumpie wrote:

Antibody-drug conjugates in breast cancer: the chemotherapy of the future?

Current Opinion in Oncology

Abstract

Antibody-drug conjugates (ADCs) represent an interesting new class of anticancer agents, capable of exploiting the specificity of monoclonal antibodies toward cellular-antigens for a targeted release of potent cytotoxic drugs, with a potential increased activity and reduced toxicity compared with traditional chemotherapies. The aim of this article is to review the efficacy and safety of ADCs in breast cancer. Following the approval of T-DM1 both in early and advanced human epidermal growth factor receptor 2 (HER2)-positive breast cancer, novel anti-HER2 ADCs have been investigated. Some of these compounds, such as the recently FDA-approved trastuzumab deruxtecan, have shown relevant activity in T-DM1-pretreated patients, possibly thanks to the so-called bystander effect, namely the ability to exert cytotoxic activity also against antigen-negative cells. Such feature allows to overcome the HER2 intratumoral heterogeneity in breast cancer and could explain in the preliminary activity demonstrated also in HER2-low breast cancers. However, several ADCs targeting other cancer-associated antigens than HER2 are under development, representing a promising strategy for the treatment of triple-negative tumors, exemplified by the encouraging results of sacituzumab govitecan. ADCs are innovative and effective therapeutic drugs in breast cancer. Research efforts are ongoing to identify novel targets and combination with other treatment modalities, particularly with immunotherapy, to further improve patients' outcomes.

https://www.meta.org/papers/antibodydrug-conjugate...

DOI: 10.1097/cco.0000000000000656


"We must be willing to let go of the life we have planned, so as to have the life that is waiting for us." "If adventures will not befall a young lady in her own village, she must seek them abroad." "Buy the ticket, take the ride." Dx 2015, DCIS/IDC, Right, 3cm, Stage IIA, Grade 3, 0/1 nodes, ER-/PR-, HER2+ (IHC) Chemotherapy 1/14/2016 Cytoxan (cyclophosphamide), Taxotere (docetaxel) Targeted Therapy 1/14/2016 Herceptin (trastuzumab) Dx 2017, IDC, Stage IV, metastasized to liver, ER-/PR-, HER2+ Surgery Lumpectomy: Right Surgery Lumpectomy: Right Radiation Therapy Whole-breast: Breast
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Jul 16, 2020 04:11PM santabarbarian wrote:

As always, Lumpie, we appreciate you!!!!! Heart

pCR after neoadjuvant chemo w/ integrative practices; Proton rads. Dx 7/13/2018, IDC, Left, 3cm, Stage IIB, Grade 3, ER-/PR-, HER2- (FISH) Chemotherapy 8/13/2018 Carboplatin (Paraplatin), Taxotere (docetaxel) Surgery 12/27/2018 Lumpectomy: Left Radiation Therapy 2/11/2019 Whole-breast: Breast, Lymph nodes
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Jul 18, 2020 06:03PM Lumpie wrote:

T-DM1 in Patients With HER2-Positive Metastatic Breast Cancer and Brain Metastases
Annals of Oncology
  • This exploratory final analysis of a phase IIIb trial was designed to evaluate the benefit of trastuzumab emtansine (T-DM1) for patients with HER2-positive breast cancer and brain metastases. Reduction in the sum of major diameters of brain metastases >30% occurred in 42.9% of patients. Significant intracranial responses were observed among 49.3% of those who had not received brain metastasis–directed radiotherapy.
  • T-DM1 has good activity in this population, and further study is warranted.
CONCLUSION: This exploratory analysis of patients with HER2-positive MBC and BM enrolled in a prospective clinical trial shows that T-DM1 is active and well-tolerated in this population. T-DM1 should be explored further in this setting.

https://www.practiceupdate.com/C/103466/56?elsca1=emc_enews_topic-alert

https://www.annalsofoncology.org/article/S0923-7534(20)39930-0/fulltext#%20

DOI:https://doi.org/10.1016/j.annonc.2020.06.020

"We must be willing to let go of the life we have planned, so as to have the life that is waiting for us." "If adventures will not befall a young lady in her own village, she must seek them abroad." "Buy the ticket, take the ride." Dx 2015, DCIS/IDC, Right, 3cm, Stage IIA, Grade 3, 0/1 nodes, ER-/PR-, HER2+ (IHC) Chemotherapy 1/14/2016 Cytoxan (cyclophosphamide), Taxotere (docetaxel) Targeted Therapy 1/14/2016 Herceptin (trastuzumab) Dx 2017, IDC, Stage IV, metastasized to liver, ER-/PR-, HER2+ Surgery Lumpectomy: Right Surgery Lumpectomy: Right Radiation Therapy Whole-breast: Breast
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Jul 18, 2020 06:39PM AlabamaDee wrote:

I found this article about specific mutations

MRE11-RAD50-NBS1 complex alterations and DNA damage response: implications for cancer treatment

https://molecular-cancer.biomedcentral.com/articles/10.1186/s12943-019-1100-5

I’m sharing it with my MO because I have MRE11a somatic mutation.

Dee

Primary neuroendocrine breast cancer Dx 5/23/2013, Right, 1cm, Stage IIB, Grade 2, 1/22 nodes, ER+/PR+, HER2- (FISH) Chemotherapy 7/29/2013 Cytoxan (cyclophosphamide), Taxotere (docetaxel) Dx 4/2019, Stage IV, metastasized to liver, ER+/PR+, HER2- Chemotherapy Doxil (doxorubicin) Targeted Therapy Afinitor (everolimus) Hormonal Therapy Faslodex (fulvestrant) Hormonal Therapy Arimidex (anastrozole), Aromasin (exemestane), Fareston (toremifene), Femara (letrozole) Hormonal Therapy Faslodex (fulvestrant) Targeted Therapy Verzenio Chemotherapy Xeloda (capecitabine)
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Jul 29, 2020 12:40PM debbew wrote:

'Liquid biopsy' tech contributes to successful clinical trial for detecting breast cancer recurrence

"These circulating markers were more predictive of relapse than any other commonly used clinical marker on the planet," Radovich said. "It's more predictive than tumor size, grade, stage or lymph node status."

"This is the largest clinical study ever published on the use of circulating markers and minimal residual disease," Radovich said. "This really puts it on the map."

https://www.purdue.edu/newsroom/releases/2020/Q3/liquid-biopsy-tech-contributes-to-successful-clinical-trial-for-detecting-breast-cancer-recurrence.html

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Jul 29, 2020 02:34PM morrigan_2575 wrote:

fascinating

Dx 1/20/2020, DCIS/IDC, Right, 4cm, Stage IIA, Grade 2, ER+/PR+, HER2+ (IHC) Chemotherapy 2/5/2020 Carboplatin (Paraplatin), Taxotere (docetaxel) Targeted Therapy 2/5/2020 Herceptin (trastuzumab) Targeted Therapy 2/5/2020 Perjeta (pertuzumab) Dx 6/19/2020, DCIS/IDC, Right, <1cm, Stage IA, Grade 2, 1/3 nodes, ER+/PR+, HER2+ Surgery 6/19/2020 Mastectomy: Left, Right; Reconstruction (left): Tissue expander placement; Reconstruction (right): Tissue expander placement Targeted Therapy 7/6/2020 Kadcyla (T-DM1, ado-trastuzumab) Radiation Therapy 8/10/2020 Whole-breast: Breast, Lymph nodes, Chest wall
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Jul 29, 2020 04:33PM AlabamaDee wrote:

I’m glad liquid biopsies are getting traction!

I have had 2 liquid biopsies with zero results, since metastatic. Very odd but I guess it happens. Had to move onto a tissue biopsy.

Dee

Primary neuroendocrine breast cancer Dx 5/23/2013, Right, 1cm, Stage IIB, Grade 2, 1/22 nodes, ER+/PR+, HER2- (FISH) Chemotherapy 7/29/2013 Cytoxan (cyclophosphamide), Taxotere (docetaxel) Dx 4/2019, Stage IV, metastasized to liver, ER+/PR+, HER2- Chemotherapy Doxil (doxorubicin) Targeted Therapy Afinitor (everolimus) Hormonal Therapy Faslodex (fulvestrant) Hormonal Therapy Arimidex (anastrozole), Aromasin (exemestane), Fareston (toremifene), Femara (letrozole) Hormonal Therapy Faslodex (fulvestrant) Targeted Therapy Verzenio Chemotherapy Xeloda (capecitabine)
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Jul 29, 2020 09:34PM Lumpie wrote:

Neratinib Plus Capecitabine in HER2+ MBC Previously Treated With ≥2 HER2-Directed Regimens
Journal of Clinical Oncology
  • This international, randomized, phase III trial was designed to evaluate capecitabine with either neratinib (an irreversible pan-HER TKI) or lapatinib (a reversible dual EGFR and HER2 TKI) in 621 patients with HER2-positive, metastatic breast cancer, including approximately 16% with brain metastases. Patients must have been previously treated with two or more HER2-directed regimens for metastatic breast cancer, although only 35% had received prior trastuzumab, pertuzumab, and T-DM1. Neratinib plus capecitabine led to a significantly improved progression-free survival (a co-primary endpoint) compared with lapatinib plus capecitabine (HR, 0.76; mean PFS difference of 2.2 months). There was no significant difference in overall survival (a co-primary endpoint) between groups (mean, 24.0 vs 22.0 months). Time to CNS disease intervention and duration of response also favored the neratinib treatment group. Diarrhea and nausea toxicities were numerically higher in the neratinib group, but discontinuation rates and quality-of-life assessments were similar.
  • This trial is the first to demonstrate superior clinical outcomes of a particular HER2-directed TKI compared with another in the metastatic setting, and establishes neratinib plus capecitabine as an appropriate treatment option for this patient population.
https://www.practiceupdate.com/C/103785/56?elsca1=emc_enews_topic-alert
https://ascopubs.org/doi/10.1200/JCO.20.00147
DOI: 10.1200/JCO.20.00147 Journal of Clinical Oncology

"We must be willing to let go of the life we have planned, so as to have the life that is waiting for us." "If adventures will not befall a young lady in her own village, she must seek them abroad." "Buy the ticket, take the ride." Dx 2015, DCIS/IDC, Right, 3cm, Stage IIA, Grade 3, 0/1 nodes, ER-/PR-, HER2+ (IHC) Chemotherapy 1/14/2016 Cytoxan (cyclophosphamide), Taxotere (docetaxel) Targeted Therapy 1/14/2016 Herceptin (trastuzumab) Dx 2017, IDC, Stage IV, metastasized to liver, ER-/PR-, HER2+ Surgery Lumpectomy: Right Surgery Lumpectomy: Right Radiation Therapy Whole-breast: Breast
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Jul 30, 2020 01:32AM Bliss58 wrote:

Fascinating about the liquid biopsies. Thanks, Debbie for sharing.

Thanks too, Lumpie, for the Neratinib trial. Always on the lookout for tx possibilities.

Dx at 56 06/2015, IDC left, 4cm, de novo mets to bone; dx 04/2020 progression to liver. Dx 6/1/2015, IDC, Left, 4cm, Stage IIIA, Grade 2, ER+/PR+, HER2+ (FISH) Dx 6/30/2015, Stage IV, metastasized to bone Radiation Therapy 12/16/2015 External: Bone Surgery 2/17/2016 Lymph node removal: Sentinel; Mastectomy: Left Radiation Therapy 5/9/2016 External: Lymph nodes, Chest wall Hormonal Therapy 2/1/2018 Aromasin (exemestane) Dx 4/2020, IDC, Stage IV, metastasized to liver, Grade 3, ER+/PR+, HER2+ (IHC)
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Jul 30, 2020 02:14AM - edited Jul 30, 2020 02:24AM by Gussy

Lumpie I ran across this today and thought it might be of interest to someone.

https://www.goodnewsnetwork.org/drug-that-can-stop-a-dozen-untreatable-cancers-gets-approval-and-company-vows-to-help-every-patient-afford-it/

Here's another https://www.goodnewsnetwork.org/cancer-vaccine-eliminates-97-tumors-amazing-success-human-trials-next/

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Jul 30, 2020 02:58AM Lumpie wrote:

Gussy: Thanks for sharing that - it does sound interesting.

For others who want highlights:

Larotrectinib is an oral drug that received accelerated breakthrough status after it displayed remarkable success in treating adult and pediatric cancers that currently have no satisfactory alternative treatments or have progressed following treatment. This is the second ever FDA-approved drug that treats cancers based on a certain genetic trait, regardless of the patient's age or cancer type, and it is the first drug to ever treat cancers that contain the specific NTRK gene that is present in several common forms of adult cancer and many forms of rare pediatric cancers. NTRK fusions are rare, but can occur in salivary gland, lung, breast, and thyroid cancers, as well as soft tissue sarcoma – and prior to this week's FDA approval, there had been no treatment for many of the cancers that frequently expressed this mutation.

Here is the FDA announcement: https://www.fda.gov/news-events/press-announcements/fda-approves-oncology-drug-targets-key-genetic-driver-cancer-rather-specific-type-tumor


"We must be willing to let go of the life we have planned, so as to have the life that is waiting for us." "If adventures will not befall a young lady in her own village, she must seek them abroad." "Buy the ticket, take the ride." Dx 2015, DCIS/IDC, Right, 3cm, Stage IIA, Grade 3, 0/1 nodes, ER-/PR-, HER2+ (IHC) Chemotherapy 1/14/2016 Cytoxan (cyclophosphamide), Taxotere (docetaxel) Targeted Therapy 1/14/2016 Herceptin (trastuzumab) Dx 2017, IDC, Stage IV, metastasized to liver, ER-/PR-, HER2+ Surgery Lumpectomy: Right Surgery Lumpectomy: Right Radiation Therapy Whole-breast: Breast
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Jul 30, 2020 03:30AM moth wrote:

Lumpie, do you know if any of the common genetic tests (foundation etc) look for the mutation that Larotrectinib targets?

Seriously???? “Sometimes the future changes quickly and completely and we’re left with only the choice of what to do next." nevertellmetheodds2017.tumblr.... Dx 12/2017, IDC, Left, 1cm, Stage IA, Grade 3, 0/5 nodes, ER-/PR-, HER2- (IHC) Surgery 12/12/2017 Lumpectomy: Left; Lymph node removal: Sentinel Chemotherapy 2/14/2018 AC + T (Taxol) Radiation Therapy 8/13/2018 Whole-breast: Breast Dx 2/2020, IDC, Stage IV, metastasized to liver/lungs, Grade 3, ER-/PR-, HER2- Chemotherapy 3/18/2020 Taxol (paclitaxel) Immunotherapy 3/19/2020 Tecentriq (atezolizumab)
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Jul 30, 2020 05:06AM - edited Jul 30, 2020 05:16AM by Lumpie

Yes. Looks like Foundation One screens for it.

Here is their list:

https://assets.ctfassets.net/w98cd481qyp0/YqqKHaqQmFeqc5ueQk48w/0a34fcdaa3a71dbe460cdcb01cebe8ad/F1CDx_Technical_Specifications_072020.pdf

I also found all 3 NTRK alterations on the Strata Oncology test list - so it appears that Strata tests for these alterations as well.

Addendum: These tests generally recommend drugs that treat cancer with the genomic finding. So it would be interesting to hear whether this drug is now being recommended. I looked at my results from Strata but, since I did not have any of these alterations, I didn't get any associated recommendations. Strata (in theory) tells you drugs in clinical trial for the alteration, but... that part did not appear to be a perfect process. I know of one drug off the top of my head that was in stage 3 trials at the time my test was run but was left off the list of clinical trial drugs (DS-8201a AKA Enhertu). In fact, they did not recommend any clinical trial drugs. In fairness, Strata was still in clinical trial phase at that point so maybe they had not fully implemented that function yet.

"We must be willing to let go of the life we have planned, so as to have the life that is waiting for us." "If adventures will not befall a young lady in her own village, she must seek them abroad." "Buy the ticket, take the ride." Dx 2015, DCIS/IDC, Right, 3cm, Stage IIA, Grade 3, 0/1 nodes, ER-/PR-, HER2+ (IHC) Chemotherapy 1/14/2016 Cytoxan (cyclophosphamide), Taxotere (docetaxel) Targeted Therapy 1/14/2016 Herceptin (trastuzumab) Dx 2017, IDC, Stage IV, metastasized to liver, ER-/PR-, HER2+ Surgery Lumpectomy: Right Surgery Lumpectomy: Right Radiation Therapy Whole-breast: Breast
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Jul 30, 2020 06:26AM moth wrote:

Thank you! You're a gem keeping us utd on all this!

Seriously???? “Sometimes the future changes quickly and completely and we’re left with only the choice of what to do next." nevertellmetheodds2017.tumblr.... Dx 12/2017, IDC, Left, 1cm, Stage IA, Grade 3, 0/5 nodes, ER-/PR-, HER2- (IHC) Surgery 12/12/2017 Lumpectomy: Left; Lymph node removal: Sentinel Chemotherapy 2/14/2018 AC + T (Taxol) Radiation Therapy 8/13/2018 Whole-breast: Breast Dx 2/2020, IDC, Stage IV, metastasized to liver/lungs, Grade 3, ER-/PR-, HER2- Chemotherapy 3/18/2020 Taxol (paclitaxel) Immunotherapy 3/19/2020 Tecentriq (atezolizumab)
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Jul 30, 2020 11:38AM JoynerL wrote:

Lumpie, thanks so much for this.

Two things: I went back and checked the list of genes for which Foundation One tested in Jan of 2019 on my own results, and it appears that the number is the current number tested is the same on the link you provided. I was hoping that they might have added a lot of new genes, but it doesn't appear to be the case. Here's the list from my Jan 2019 test. Maybe I didn't look carefully enough:

Second, on my own test results, I found that I have NTRK1 amplification. I got excited and thought that this might be an option for me. However, per the article below I found, this drug works most specifically to fusions rather than other modifications:

https://www.cancernetwork.com/view/larotrectinib-demonstrates-limited-benefit-patients-ntrk-alterations

--Lynn Dx 12/1990, IDC, Left, <1cm, Stage IIA, ER+ Surgery 1/2/1991 Lymph node removal: Underarm/Axillary; Mastectomy: Left; Reconstruction (left): Nipple reconstruction, Saline implant Chemotherapy 1/15/1991 CMF Hormonal Therapy 6/30/1991 Tamoxifen pills (Nolvadex, Apo-Tamox, Tamofen, Tamone) Hormonal Therapy 10/31/2002 Evista (raloxifene) Dx 2/9/2017, IDC, Left, 1cm, Stage IV, metastasized to bone, ER+/PR-, HER2- Hormonal Therapy 3/5/2017 Faslodex (fulvestrant) Targeted Therapy 3/5/2017 Ibrance (palbociclib) Chemotherapy 1/17/2019 Xeloda (capecitabine) Targeted Therapy
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Jul 30, 2020 03:59PM BevJen wrote:

Interesting article from Science News today about the effectiveness of an immunotherapy plus a vaccine currently being trialed (phase 2) at Duke -- currently for Her2+ use.

https://scienmag.com/investigational-breast-cancer...

Dx 11/2003, ILC, Left, Stage IIIC, ER+/PR+, HER2- Dx 6/2006, ILC, Stage IV, metastasized to other, ER+ Dx 5/2019, ILC, Stage IV, metastasized to liver, ER+/PR+, HER2- Surgery 7/5/2019 Targeted Therapy 8/1/2019 Ibrance (palbociclib) Radiation Therapy Surgery Lymph node removal: Left, Sentinel; Mastectomy: Left, Right; Reconstruction (left): Pedicled TRAM flap; Reconstruction (right): Pedicled TRAM flap Chemotherapy TAC Hormonal Therapy Faslodex (fulvestrant) Hormonal Therapy Tamoxifen pills (Nolvadex, Apo-Tamox, Tamofen, Tamone) Surgery Lymph node removal; Mastectomy; Reconstruction (left): Pedicled TRAM flap; Reconstruction (right): Pedicled TRAM flap Hormonal Therapy Femara (letrozole)
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Jul 30, 2020 06:40PM BlueGirlRedState wrote:

JoynerL - That list is huge. I need to go back and look at results from genetic test my DR ordered Sept 2019. No known markers were found, but I thought she said 20-30 known markers were looked at. Your list looks much larger. I think she said the test was specific to BC. Insurance so far has denied to claim, saying it is not relevant to diagnosis or treatment. I think the lab is going to pick up most of the cost.

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