Good News re: CDK4/6 Inhibitors & Overall Survival

Schnauzer, there's an excellent recap here: http://www.ahdbonline.com/articles/2534-abemaciclib-verzenio-a-novel-cdk4-6-inhibitor-in-the-treatment-of-hormone-receptor-positive-her2-negative-advanced-breast-cancer

Candy, The Ibrance OS data came out last year, which are included in my Guide and pasted below. Your questions about successive treatments would best be answered by your medical team. That said, Ibrance and Kisqali are very similar; Verzenio works somewhat differently and may be considered as a successor drug.

Furthermore, the PALOMAIII study revealed that the combination of Ibrance and Faslodex resulted in a clinically meaningful improvement in Overall Survival (not just Progression Free Survival) among women with hormone receptor-positive, HER2-negative breast cancer whose disease relapsed or progressed on hormonal therapy. The Ibrance/Faslodex regimen extended median Overall Survival (OS) by an absolute difference of 6.9 months (34.9 months on the combination arm vs. 28 months on the Faslodex-only arm). Researchers observed even greater OS benefits among women with endocrine-sensitive disease (median, 39.7 months on the combination arm vs. 29.7 months on the Faslodex-only arm) and those with non-visceral disease (median, 46.9 months on the combination arm vs. 35.4 months on the Faslodex-only arm). From: https://www.healio.com/hematology-oncology/breast-cancer/news/online/{cd3e8a02-e13e-4ad4-a2d2-1be2a182b4f7}/addition-of-palbociclib-to-fulvestrant-extends-os-among-certain-women-with-advanced-breast-cancer

Cure-ious, indeed there are mixed opinions about second- and third- line therapies. Here's the lineup I created for postmenopausal HR+, HER2- patients based upon 2019 NCCN Guidelines, which was reviewed and approved by Dr. Kevin Kalinsky, a MO at Columbia Presbyterian Hospital in NYC.

FDA-Approved First Line Hormonal and Targeted Treatment Options for Postmenopausal Patients in the US (depending upon what, if any, recent treatments the patient may have had in the adjuvant setting):

An Aromatase Inhibitor (Letrozole, Arimidex, or Aromasin) either alone or in combination with a CDK4/6 inhibitor (Ibrance, Kisqali, or Verzenio

Faslodex either alone or with a CDK4/6 inhibitor (Ibrance, Kisqali, or Verzenio)

Faslodex with Arimidex A recent study (NCT00075764) reported that postmenopausal 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. Therefore, this combination may be worth discussing with one's doctor.

Tamoxifen or Fareston alone (rarely used as a first-line therapy).

At a presentation delivered in April 2019 by Medical Oncologist Dr. Neil Vasan of Memorial Sloan Kettering, the following general guideline regarding first-line therapy was offered regarding patients who had previously been diagnosed with early stage breast cancer:

• 1. If the patient's "disease-free interval" (the amount of time since the patient completed adjuvant endocrine therapy for their earlier-stage disease) has been more than 1 year, use an aromatase inhibitor alone, or an aromatase inhibitor combined with a CDK4/6 inhibitor
• 2. If the patient's disease-free interval has been less than 1 year, use Faslodex alone, or Faslodex combined with a CDK4/6 inhibitor

FDA-Approved Second Line Hormonal and Targeted Treatment Options for Postmenopausal Patients in the US (depending upon prior treatment):

Possibly any of the above therapies.

Afinitor with either an Aromatase Inhibitor, Faslodex, or Tamoxifen.

Verzenio alone (after disease progression on endocrine therapy and prior chemotherapy for MBC).

Piqray in combination with Faslodex if the cancer has a PI3K mutation

FDA-Approved Third Line and Above Hormonal and Targeted Treatment Options for Postmenopausal Patients in the US (depending upon prior treatment):

• Possibly any of the above therapies (although not all options are widely used in a third or later line setting).
• Either Ethinyl Estradiol, Megace (Megestrol Acetate), or Halotestin (Fluoxymesterone).

Chemotherapy is usually prescribed after 2 to 3 lines of endocrine therapy have stopped working. 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.

Furthermore:

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) and Rozlytrek (Entrectinib) – oral tyrosine kinase inhibitors that act as an "on" or "off" switch in many cellular functions – are FDA-approved options. NTRK fusions are extremely rare, occurring in only about 0.5–1% of common cancers.

Anewbreath, you are welcome! Faslodex is a SERD (Selective Estrogen Degrader/Downregulator) and it works differently than Aromatase Inhibitors such as Letrozole, Arimidex, and Aromasin. For more information, I'd strongly suggest getting my Guide!

Anewbreath, please obtain the updated .pdf or the book. Much has changed and continues to do so. I keep all formats (paperback, eBook and .pdf) updated.