FDA-Approved Treatments for HR+, HER2- Premenopausal Patients

[Bestbird]

Last week, I posted a list of FDA-approved treatments for HR+, HER2- postmenopausal US patients. Below is the list of FDA-approved treatments for HR+, HER2- premenopausal patients. I finalized this list of treatments with a Medical Oncologist at Columbia Presbyterian Hospital in NY, and it is available (along with information about cutting edge MBC research, symptom and side effect mitigation, clinical trials, and more) in my book, "The Insider's Guide to Metastatic Breast Cancer" which is available as a paperback and eBook, and also a complimentary .pdf. For more information, please visit: insidersguidembc.com/about

In premenopausal women – and also in men - a Luteinizing Hormone-Releasing Hormone (LHRH) agonist such as Zoladex (Goserelin), Lupron (Leuprolide) or Trelstar (Triptorelin) is recommended along with hormonal (endocrine) therapy. In females, LHRH agonists work by telling the pituitary gland located in the brain to stop producing luteinizing hormone (which stimulates the ovaries to release estrogen). This process of limiting the production of estrogen is referred to as “ovarian suppression.” In males, these LHRH drugs are sometimes referred to as Gonadotropin Releasing Hormone (GnRH) agonists which suppress the testicular production of estrogen. All three medications are administered as injections and should generally be used by hormone receptor positive men and premenopausal women in combination with hormonal therapy. (Instead of initially taking an LHRH agonist, some hormone receptor positive premenopausal patients may opt to undergo an oophorectomy, which involves the surgical removal of both ovaries - referred to as “ovarian ablation” - at which point they become postmenopausal and would follow the endocrine treatment guidelines for postmenopausal women).

The sequence of providing hormonal (endocrine) therapy for premenopausal patients will vary, as much of it depends upon what - if any - hormonal therapy drugs the patient has previously taken in the adjuvant and/or metastatic setting, and how recently they were administered.

First Line Hormonal and Targeted Treatment Options for Premenopausal Patients in the US:

•The combination of an Aromatase Inhibitor (AI) such as Letrozole, Arimidex, or Aromasin with a CDK4/6 inhibitor such as Ibrance, Kisqali or Verzenio can serve as a highly effective initial treatment along with an LHRH agonist. In the recent MONALEESA-7 study, the combination of Kisqali with endocrine therapy demonstrated an estimated Overall Survival (OS) rate of 70.2% at 42 months compared with 46.0% for placebo and endocrine therapy.

•An Aromatase Inhibitor without a CDK4/6 inhibitor (but with an LHRH agonist).

•Faslodex (Fulvestrant) either with a CDK4/6 inhibitor or alone (but with an LHRH agonist.

•Faslodex and Arimidex: The clinical trial NCT00075764 reported that patients taking Faslodex and Arimidex as initial endocrine therapy had a median Overall Survival (OS) of 49.8 months compared with 42 months in the Arimidex-only arm, which is the longest ever reported for this type of patient. Although all study participants were postmenopausal women, this combination (along with an LHRH agonist) may be worth discussing with one’s doctor.

•Tamoxifen (Nolvadex) or Fareston (Toremifene) with or without an LHRH agonist is also a first line therapeutic option. Combining ovarian suppression and Tamoxifen or Fareston improves survival over either treatment alone.

After progression if the patient still has her ovaries, an oophorectomy may appropriate because it will remove a key source of estrogen from being produced by the body. After an oophorectomy, the patient is considered postmenopausal and would follow the hormonal therapy guidelines for postmenopausal patients. For patients deciding against an oophorectomy, the therapies below can be considered .

Second Line Hormonal and Targeted Treatment Options for Premenopausal Patients in the US depend upon what endocrine therapy the patient has previously taken:

•Possibly any of the above therapies.

•With an LHRH agonist, Afinitor (Everolimus) can be taken in combination with either an Aromatase Inhibitor (Letrozole, Arimidex, or Aromasin), or with Faslodex, or with Tamoxifen.

Later-Line Hormonal and Targeted Treatment Options for Premenopausal Patients in the US:

Patients may want to reconsider having an oophorectomy and possibly taking different endocrine therapy. Another option is chemotherapy, which is usually prescribed after endocrine therapies have stopped working (usually after 2 to 3 hormonal therapies have been tried and stopped). A clinical trial may also be a consideration. Once the cancer has regressed or stabilized, it may be possible to go back on endocrine therapy if sufficient time has elapsed and if the initial response to endocrine therapy had been favorable.

DID YOU KNOW?

If you have bone metastases, you should receive a bone-directed therapy such as Xgeva (Denosumab) or Zometa (Zoledronic acid) in addition to your other therapy.

If you have a germline BRCA mutation, you may want to speak with your doctor about taking a PARP inhibitor such as Talazoparib (Talzenna) or Olaparib (Lynparza), which are FDA-approved for HER2 negative MBC patients with BRCA mutations.

If your cancer has microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) characteristics (which are very rare), and if you’ve progressed on prior therapy and have no satisfactory treatment options, Keytruda (a PD-1 inhibitor also known as Pembrolizumab), is an FDA-approved option.

If your cancer has a Neurotrophic Receptor Tyrosine Kinase (NTRK) gene fusion without a known acquired resistance mutation, and if you’ve progressed on prior therapy and have no satisfactory treatment options, Larotrectinib (Vitrakvi) - an oral tyrosine kinase inhibitor that acts as an "on" or "off" switch in many cellular functions – is an FDA-approved option. NTRK fusions are extremely rare, occurring in only about 0.5–1% of common cancers.

*The above hormonal treatment options are recommended for premenopausal patients who are not experiencing “visceral crisis” (severe organ dysfunction and rapid progression of disease). For patients who have visceral crisis, chemotherapy may be used straightaway to control the disease, after which hormonal therapy may be a viable option.

[kearnan]

One would need a medical degree to digest the above LOL. That is why I have my onco. I trust her to have the knowledge necessary to help me with my treatment.