Drugs for Her 2 Neu

Drugs and Trial information
If you see a mistake in my list or have something to add - Please let me know. Thank you.

From the 2020 ASCO - American Society of Clinical Oncology

Currently there is no standard of care after 2nd line drug Kadcyla - ado-trautzumab emtansine (TDM1).

DRUGS used for Her 2 neu + Breast Cancer
  
Brand Name            Generic name
Taxol                  =      paclitaxel
Taxotere            =      docetaxol
Xeloda               =      capecitabine
Tykerb               =       lapatinab - (small molecule that passes the blood brain barrier)
Herceptin         =      trastuzumab
Perjeta               =       pertuzumab
Kadcyla-TDM1 =      ado-trastuzumab emtansine (a do tras TU zoo mab emtanseen)
Nerlynx             =     neratinib (Puma Biotechnology)FDA approved early stage 2017
Herceptin Hylecta (injection) = trastuzumab & hyluroidase-oysk used with Taxol 2-2019
Tukysa              =       tucatinib (ONT380)- approved for heavily treated HER2 + patients, also with brain mets--                                    April 2020, approved by FDA

Other Chemo drugs that might be used. Chemo drugs may be paired with Herceptin, some probably dependent on ER status.

Navelbine         =        vinorelbine
Gemzar             =        gemcitabine
Paraplatin        =        carboplatin
Avastin             =        bevacizumab
Halavan             =        eribulin
 
Combinations:
FIRST-LINE THERAPY 
Taxotere + Carboplatin + Herceptin
Taxotere + Herceptin + Perjeta
Taxol + Herceptin
Herceptin + Perjeta
Herceptin Hylecta (injection) with Taxol FDA approved 2-2019 (Genetech)
ASCO (American Society of Clinical Oncology) recommends stopping the taxane after 6 months of stable disease and continuing Perjeta + Herceptin.
If progression occurs without the taxane, it is recommended that the taxane is resumed or to start second-line therapy. 
Current Study:  PERUSE study evaluating Perjeta, Herceptin, and a taxane.
Taxanes are: Paclitaxel, (Taxol), Docetaxel (Taxotere) or Nabpaclitaxel (Abraxane)

SECOND-LINE THERAPY
T-DM1 (Kadcyla) alone

THIRD-LINE THERAPY and LATER LINES-no recommended regimens
Tykerb (lapatinab) + Xeloda (capecitabine)
Tykerb + Herceptin
Tykerb + Letrozole (Aromatase Inhibitor usually used with hormone positive cancer.)
Tukysa (tucatinib-approved 2020 for late stage) + Herceptin + Xeloda
Nerlynx             =     neratinib (Puma Biotechnology)FDA approved early stage 2017
Herceptin Hylecta (injection) = trastuzumab & hyluroidase-oysk used with Taxol 2-2019

Her 2 neu drug trials
From ASCOpost.com 2018 conference

Monoclonal Antibodies
*Margetuximab
*New - PRS343, targets immune receptor CD137

Antibody - Drug Conjugates
*Trastuzumab Deruxtecan (DS-8201)
*New - ARX788 linked to a microtubule--disrupting agent

Tyronsine Kinase Inhibitors
*Pyrotinib
*Tucatinib

(Below same as above-- Taken from website) From ASCOpost.com 2018 conference
Monoclonal Antibodies
*Margetuximab (MGAH22) target same as Herceptin
*New - PRS343, targets immunne receptor CD137
Antibody - Drug Conjugates
*Trastuzumab Deruxtecan (DS-8201) antibody drug conjugate
*New - ARX788 linked to a microtubule--disrupting agent

Tyronsine Kinase Inhibitors
*Pyrotinib
*Tucatinib (ONT-380)

Update of HER2+ drugs March 2018 -- (drugs mentioned above)
Hurvitz Heralds Next HER2+ Breast Cancer Breakthroughs 2018 Miami Breast Cancer Conference March 10, 2018.
Drugs: Tucatinib (ONT-380)-approved April 2020 for late stage
Margetuximab (MGAH22) target same as Herceptin,
Trastuzumab Deruxtecan (DS-8201) antibody drug conjugate,
Pyrotinib.

From Facebook She and Us and Her 2 Group--Valynda Planeta in ZR25 Trial at MD Anderson, Houston Texas. It is a biphasic antibody like Herceptin and Perjeta but stronger.

December 2017 Trial Pyrotinib and Capecitabine Now in Phase III trial. This combination is being compared to Capecitabine (Xeloda) and Lapatinab (Tykerb)

September 2017
Trial-not sure where, but in USA-ribociclib (LEE099) with herceptin or TDM-1(Kadcyla), phase Ib/II CDK 4/6 inhibitor

Updated info at ASCO 2018 conference
FDA Grants Breakthrough Therapy Desgination in 2017 to DS-8201 for Her2+ see here
DS-8201 (Trastuzumab Deruxtecan) carries a payload - a topoisomerase inhibitor - as opposed to a tubulin inhibitor used in TDM1. delivers chemotherapy by a monoclonal antibody-- works like TDM1--ado-trautzumab emtansine. (ADC) antibody drug conjugate for metastatic patients after resistance of refractory to TDM1
Designation granted after stage 1 dosing trial (ClinicalTrials.gov Identifier: NCT02564900
Phase II study called DESTINY-Breast studying safety and efficacy. here
Pharmaceutical Company Daiichi Sankyo conducting trial.   

8-201 7
Pyrotinib - (oral, irreversible pan-ErbB receptor tyosine knase inhibitor against EGRF/HER1, HER2, and HER4) Phase I, targets HER1, 2, 4 find it here. Patients with mutations in PIK3CA and TP53 seem to do better. Out of 36 patients 50% had partial response. Medium duration of response was 32.4 weeks, medium progression free response 35.4 weeks. (Not very long but I will take what I can get.) 

6-2017 
Nerlynx (Puma Biotechnology) also known as Neratinib, FDA approved June 2017 for early stage treatment after Herceptin. Targets proteins that promote cell growth: EGFRs, HER2 and HER4.  From March 2018 (Susan Jacobson's post on She and Us and HER2 group) Miami Breast Cancer Conference--This drug is most effective for those with a lower-scoring HER2+ amount of protein. 

2020 April-- Tucatinib APPROVED by FDA, taken with Trastuzumab and Capecitabine
Before approval--July 2019-- HER 2 CLIMB Study Tucatinib plus Herceptin or Capecitabine
ONT-380 (tucatinib) previously known as ARRY-380 (oral drug) small molecule/may treat brain metastases
New HER2 + Trial from Cascadian Therapeutics 12-2016
Tucatinib (ONT-380) -- small molecule, HER2 inhibitor, Phase 2 trial underway
info here and here 2017--Tucatinib earns fast track by FDA-- expansion of study. here
small molecules can get through blood brain barrier of brain. (From Susan Jacobson's post on She and US and HER2 group--From Miami Breast Cancer conference, Tucatinib sold to another company (?), "This drug is planned to be their star drug".)

From Cascadian Therapeutics Website: other small molecule drugs are dual inhibitors for HER1 and 2--Tykerb (lapatinib), neratinib and Gilotrif (afatinib)
Neratinib + Xeloda (Capecitabine) Study for HER2+ MBC Patients with Brain Metastases: Neratinib--orally ingested drug that crosses the blood brain barrier (BBB).  From ASCO 2017 meeting

January 2017 - onclive.com
Phase III SOPHIA trial ( NCT02492711), drug margetuximab-target same as Herceptin (on FDA Fast Track as of ASCO 2018 conference) paired with herceptin or chemotherapy of physicians choice: capecitabine, gemcitabine, vinorelbine, eribulin. Enter trial after prior treatment with herceptin, perjeta, TDM-1. Patients with stable brain metastasis are eligible. Margetuximab is a Fc modified monoclonal antibody. End goal--to see if better results than of herceptin. (from post by Susan Jacobson on She and US and HER2 group--SOPHIA trial ending enrollment at end of 2018 due to low number of participants.

12-2016
Biosimilars/biologics - drugs that are like natural substances in our bodies.
Myl-1410O, similar to Herceptin, not FDA approved yet. Dec 2016--Journal of the American Medical  Association (JAMA) publishes Phase 3 data by Mylan N.V. and Biocon LTD of efficacy of biosimilar Herceptin (Trastuzumab).
update: 1-26-18 May be now called Ogivri biosimilar to Herceptin, FDA approval Dec 2017. Not available till 2019.

11-2015
click here Medivizor Website updated Nov 2015 --"The mTOR protein is a molecule normally responsible for cell growth, division and survival. Drugs that inhibit the actions of mTOR have been the focus of recent cancer treatment research. Various mTOR inhibitors, such as everolimus (Afinitor), temsirolimus (Torisel) and sirolimus (Rapamune) are currently being investigated in clinical trials including breast cancer patients."
"Research into the use of mTOR inhibitors for the treatment of HER2-positive breast cancer patients is still in early phases. A phase one trial investigating the combination of everolimus and trastuzumab demonstrated that the combination is well tolerated and safe to use. Preliminary results from a phase II trial among recurrent breast cancer patients reported that everolimus in combination with trastuzumab and chemotherapy resulted in a stable disease (no additional growth of the cancer for 6 months) in up to 62% of patients. A large, controlled, phase III trial investigating everolimus as first choice treatment for HER2-positve breast cancer patients is currently underway."

2015
Neratinib + Temsirolimus (Neratinib-may cause severe diarrhea)

A Phase I/II Trial of Temsirolimus Plus Neratinib for Patients With Metastatic HER2-Amplified or Triple Negative Breast Cancer www.clinicaltrials.gov Began April 2015, Ends Dec 2015 The phase III ExteNET trial evaluated neratinib, an oral tyrosine kinase inhibitor that blocks HER2, in patients with HER2-positive breast cancer. The 2-year invasive disease-free survival rate was 93.9% in the neratinib arm versus 91.6% with placebo, representing a 33% reduction in the risk of recurrence (HR = 0.67; P = .009). However, 95.4% of patients treated with neratinib experienced all-grade diarrhea (39.9% were grade 3/4), points out Rugo. The rates of diarrhea seen in the ExteNET study could be related to an initial lack of antidiarrheal therapy, which caused immediate diarrhea in the majority of patients. The management of diarrhea is now better understood, and the current standard includes routine prophylaxis, says Rugo. Studies continue to assess neratininb, and there is interest in combining neratinib with trastuzumab and pertuzumab, adds Rugo. - See more at: http://www.onclive.com/insights/breast-cancer-treatment/anti-human-epidermal-growth-factor-receptor-2-her2-treatments-in-breast-cancer#sthash.WBQCRk72.dpuf The phase III ExteNET trial evaluated neratinib, an oral tyrosine kinase inhibitor that blocks HER2, in patients with HER2-positive breast cancer. The 2-year invasive disease-free survival rate was 93.9% in the neratinib arm versus 91.6% with placebo, representing a 33% reduction in the risk of recurrence (HR = 0.67; P = .009). However, 95.4% of patients treated with neratinib experienced all-grade diarrhea (39.9% were grade 3/4), points out Rugo. The rates of diarrhea seen in the ExteNET study could be related to an initial lack of antidiarrheal therapy, which caused immediate diarrhea in the majority of patients. The management of diarrhea is now better understood, and the current standard includes routine prophylaxis, says Rugo. Studies continue to assess neratininb, and there is interest in combining neratinib with trastuzumab and pertuzumab, adds Rugo. - See more at: http://www.onclive.com/insights/breast-cancer-treatment/anti-human-epidermal-growth-factor-receptor-2-her2-treatments-in-breast-cancer#sthash.WBQCRk72.dpuf The phase III ExteNET trial evaluated neratinib, an oral tyrosine kinase inhibitor that blocks HER2, in patients with HER2-positive breast cancer. The 2-year invasive disease-free survival rate was 93.9% in the neratinib arm versus 91.6% with placebo, representing a 33% reduction in the risk of recurrence (HR = 0.67; P = .009). However, 95.4% of patients treated with neratinib experienced all-grade diarrhea (39.9% were grade 3/4), points out Rugo. The rates of diarrhea seen in the ExteNET study could be related to an initial lack of antidiarrheal therapy, which caused immediate diarrhea in the majority of patients. The management of diarrhea is now better understood, and the current standard includes routine prophylaxis, says Rugo. Studies continue to assess neratininb, and there is interest in combining neratinib with trastuzumab and pertuzumab, adds Rugo. - See more at: http://www.onclive.com/insights/breast-cancer-treatment/anti-human-epidermal-growth-factor-receptor-2-her2-treatments-in-breast-cancer#sthash.WBQCRk72.dpuf From http://www.onclive.com Phase III ExteNET trial - looked at Neratinib (an oral tyrosine kinase inhibitor that blocks EGFRs, and HER2 + HER4) showed a 33% reduction in risk of invasive Her 2 neu positive breast cancer after early stage treatment. Diarrhea was problematic.   For issues with diarrhea from Neratinib called PB272, see here

10-4-2015 at UNC Lineberger Cancer Center in Chapel Hill, North Carolina--Find it Here 
A four part, Phase I Dose-Escalation Study of the Combinations of Concurrent BKM120 and Capecitabine, or Concurrent BYL719 and Capecitabine, or Concurrent BKM120 and Capecitabine and Trastuzumab, or Concurrent BKM120 and Capecitabine and Lapatinib in Patients with Metastatic Breast Cancer
BKM120
CAPECITABINE
GW572016 (LAPATINIB)
HERCEPTIN (TRASTUZUMAB)
LAPATINIB
TRASTUZUMAB
TYKERB (LAPATINIB)
XELODA (CAPECITABINE) 


There are many Phase 1 and Phase 2 trials occurring. See www.cancer.gov/clinicaltrials  or   National Institutes of Health website www.clinicaltrials.gov National Institutes of Health (nih) or cancertrials.nci.nih.gov  

eratinib, an oral tyrosine kinase inhibitor that blocks HER2, in patients with HER2-positive breast cancer. - See more at: http://www.onclive.com/insights/breast-cancer-treatment/anti-human-epidermal-growth-factor-receptor-2-her2-treatments-in-breast-cancer#sthash.WBQCRk72.dpuf

More Trials:
Afatinib (Gilotrif)--small molecule

Poziotinib - oral pan-Her inhibitor in Phase II trials. 60% response rate

Agents to overcome resistance called phosphatidylinositol 3 kinase inhibitors

Neratinib + Capacitabine   vs   Lapatinib + Capecitabine

Phase 3 trials--MM302 - similar to Kadcyla in method of delivery- I learned from Sarah Merchant's blog that the main ingredient is adriamycin.

Research happening in the PI3K gene (errors in this gene) - pathway that some Her 2 neu types use:
Trials - BGT-225 & BEZ-235

 
Some of the drugs used to treat breast cancer are also used to treat other cancers. 


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