This is part 2 of our 2-part series, we call ASCO 2022: When The Dust Settles. Our senior producer Victoria Goldberg is joined by the co-host , Kate Pfitzer and the friends  of this podcast, three prominent clinicians and thought leaders in the field of breast cancer, Doctors Stephanie Graff, Sara Hurvitz,  and Kevin Kalinsky.  We’ve seen a lot of interesting data come out of 2022 ASCO in the metastatic hormone receptor-positive setting and are very eager to discuss survival data from PALOMA-2 and MONARH-3, the emergence of oral SERDs from the EMERALD trial,  and the data from a small but very interesting phase 2 MAINTAIN trial. In the next hour you will get a lot of information and some of it might be somewhat complex. So in order to make it a little less overwhelming, here is a list of questions we will attempt to answer in this episode

1. What does the new survival data from mean PALOMA-2 and MONARCH-3 trials mean for the clinicians in how they view the 3 CDK4/6 inhibitors and the impact for patients in how the treatments are selected for them?

2. We have a definitive answer to what is to be used in the first-line setting. It is one of the 3 FDA approved cdk4/6 inhibitors in combination with hormonal therapy, but what about the second-line setting. Should CDK4/6 inhibition continue after the disease progression? Will the data from the MAINTAIN trial help us answer this question?

3. What are the strategies for a patient who progresses after a CDK4/6 inhibitor. At what point should a patient be tested for acquiring ESR1 or PI3 kinase mutations? What is the role of chemotherapies and the newly approved antibody drug conjugates?

4. SERDs [selective estrogen receptor degraders], and especially oral SERDs are exciting new therapies. There has been so much hope placed in these agents. We’ve been waiting for better endocrine therapies and the opportunity to have an oral agent instead of the intermuscular fulvestrant [Faslodex]. And so We’ve been eagerly awaiting data from the EMERALD trial , which had compared the oral agent ela’cestrant with endocrine therapy of physician’s choice. Based on the results from this and other trials, what does the future look like for this class of drugs

Key Questions Answered [from the transcript]

Glossary

Novel Therapies Mentioned in the Episode

• Trastuzumab Deruxtecan (Enhertu or TdxD)

• Elacestrant (oral selective estrogen receptor degrader)

• Sacituzumab Govitecan (Trodelvy)

• CDK4/6 inhibitors - palbociclib [Ibrance], ribociclib [Kisqali] , and abemaciclib [Verzenio]

• Venetoclax - potent, selective BCL2 inhibitor that has shown promising clinical activity in pts with ER-positive and BCL2-positive MBC who have received prior endocrine therapy (VERONICA trial)

• Avelumab

Clinical Trials Mentioned in this Episode

MAINTAIN - randomized, phase II trial of fulvestrant or exemestane with or without ribociclib after progression on anti-estrogen therapy plus cyclin-dependent kinase 4/6 inhibition (CDK 4/6i) in patients (pts) with unresectable or hormone receptor–positive (HR+), HER2-negative metastatic breast cancer [NCT02632045]

EMERALD - randomized phase III trial of elacestrant (oral selective estrogen receptor degrader) Versus Standard Endocrine Therapy for Estrogen Receptor–Positive, Human Epidermal Growth Factor Receptor 2–Negative Advanced Breast Cancer[]NCT03778931

NATALEE - phase III study of ribociclib (RIBO) + endocrine therapy (ET) as adjuvant treatment in hormone receptor–positive (HR+), human epidermal growth factor receptor 2–negative (HER2–) early breast cancer (EBC) [NCT03701334]

PACE - a multicenter phase II trial randomizing pts 1:2:1 to Arm A: fulvestrant alone (with option for palbociclib monotherapy crossover at time of progression);Arm B: fulvestrant and palbociclib; or Arm C: fulvestrant, palbociclib, and avelumab.[NCT03147287]

PALLAS - randomised open-label phase III study of Palbociclib with adjuvant endocrine therapy in early breast cancer

PENELOPE-B - double-blind, placebo‐controlled, phase III study in women with hormone receptor–positive, human epidermal growth factor receptor 2–negative primary breast cancer without a pathological complete response after taxane‐containing NACT and at high risk of relapse [NCT01864746]

VERONICA -  randomized, phase II study of second-/third-line venetoclax (VEN) + fulvestrant (F) versus F alone in estrogen receptor (ER)-positive, HER2-negative, locally advanced, or metastatic breast cancer (LA/MBC) [NCT03584009]

postMONARCH - phase 3 study of abemaciclib plus fulvestrant versus placebo plus fulvestrant in patients with HR+, HER2-, metastatic breast cancer following progression on a CDK4 & 6 inhibitor and endocrine therapy [NCT05169567]

Want More?

If you have not done so already, listen to our past interviews with the guests of this episode as well as ASCO 2022-related content.

Meet the Guests of this Episode