ASCO's New Guideline for Endocrine Therapy

Tina2

Here's the latest:

http://www.medscape.com/viewarticle/864032?src=wnl...

Tina

SonnyB

Thanks for the link to the new guidelines!

Bestbird

Thank you for posting this!

The following statement has me a bit perplexed. Does this mean that letrozole or Arimidex can be given along with Faslodex?

"Combination hormone therapy with a nonsteroidal AI and fulvestrant (Faslodex, AstraZeneca) 500 mg and with a loading-dose schedule can be offered to patients who have not previously used endocrine therapy."

Longtermsurvivor

Hi Bestbird,

I wondered about that too, so found the original article for more details (see below).

I've separated one paragraph to offset the first section on the combination therapy of AIs with Fulvestrant/Faslodex as first-line treatment in MBC. Other readers might be interested in the rest of the paragraph that includes Afinitor (everolimus) and Ibrance (palbociclib).

Afinitor was drug of the year a few years back, based on PFS (progression free survival), but failed on toxicity and OS (overall survival)l.

Ibrance is similarly touted now for PFS, but I'm still wondering about toxicity/tolerability and OS data. Wish the figures could be published, so we've a better idea of the bigger picture. I notice from the Ibrance topics here, that many aren't able to continue at the 125mg dosage...so even if the study data comes in at the higher dosage, it might not be reflected at lower dosages.

MBC treatment is an art, not a science.

warmest healing wishes, Stephanie

http://jco.ascopubs.org/content/early/2016/05/19/J...

COMBINATIONS OF HORMONE THERAPY OR HORMONE THERAPY WITH TARGETED AGENTS

Existing data suggest that combinations of hormone therapy should be considered only in specific situations, although ongoing trials are evaluating additional settings and drug doses. Discordant results have been reported on combinations of the selective ER downregulator fulvestrant and aromatase inhibitors (AIs) in the first-line setting; one randomized study showed improved PFS and OS, favoring the combination over the AI alone, but another with a similar design showed equivalent PFS and OS.^12,13 Subset analysis suggested that the survival benefit was primarily observed in patients without exposure to prior endocrine therapy.

A phase II trial comparing fulvestrant with anastrozole as first-line therapy for hormone-naïve MBC demonstrated no improvement in the primary end point of clinical benefit, but subsequent follow-up suggested improved time to progression (TTP) and OS with use of fulvestrant; an ongoing phase III trial is exploring this comparison (Data Supplement 8 provides details on the FALCON [A Global Study to Compare the Effects of Fulvestrant and Arimidex in a Subset of Patients With Breast Cancer] trial [ClinicalTrials.gov identifier NCT01602380]).^14,15 Few studies have demonstrated a survival benefit for one treatment compared with another in postmenopausal patients with HR-positive MBC; for that reason, variation in sequencing or the use of combination therapy can be offered.

Hormone therapy administered in combination with agents targeted to pathways implicated in hormone resistance is under intense evaluation, with both failures and recent successes.

The mammalian target of rapamycin (mTOR) inhibitor everolimus, administered in combination with the steroidal AI exemestane in patients with progressive disease or disease resistant to nonsteroidal AIs (letrozole or anastrozole), demonstrated improved PFS compared with exemestane alone but was associated with increased toxicity and did not improve OS; these data led to US Food and Drug Administration (FDA) approval of everolimus and exemestane.^4,16

The addition of the cyclin-dependent kinase (CDK) 4/6 inhibitor palbociclib, administered as first-line therapy in combination with the nonsteroidal AI letrozole, in an open-label phase II trial also significantly improved PFS without improving OS.⁷ This combination was well tolerated, although the study was small. Accelerated approval for palbociclib was granted early in 2015, pending results from a phase III trial with a similar design (Data Supplement 8 provides details on the PALOMA-2 [Palbociclib: Ongoing Trials in the Management of Breast Cancer] trial).

Palbociclib was also studied as second-line therapy for HR-positive MBC in combination with fulvestrant in a placebo-controlled phase III trial. The addition of palbociclib significantly improved PFS, with a toxicity profile similar to that shown in the phase II trial; survival data are immature.¹⁷ Global QoL was generally maintained in the palbociclib arm, but it deteriorated in those receiving placebo. Therapy targeted to HER2 combined with hormonal agents in patients with HR-positive, HER2-positive MBC also resulted in improved PFS compared with hormonal agents alone, without improved survival.^5,6 Controversy exists about how to use these novel drugs in clinical practice. Additional agents targeting a number of pathways are in phase III trials as well (Data Supplement 8).