Overcoming Endocrine Resistance in HRpos HER2neg MBC : Pre-test

1.

Patient Case: A 67-Yr-Old Woman With de Novo MBC

A 67-yr-old woman was diagnosed with de novo metastatic breast cancer to bones 3 yr ago

At that time, bone and breast biopsy revealed adenocarcinoma ER-positive, PgR-positive, HER2-negative disease

Tumor genomics did not reveal actionable mutations

Treatment with ribociclib plus letrozole was initiated

Recent scans show disease progression in her bones

At this time, ctDNA analysis of the patient’s blood sample is performed

Which of the following is the most likely molecular alteration(s) that will be seen on ctDNA analysis?

A. ESR1 mutation only
B. ESR1 and TP53 mutations
C. PIK3CA mutation only
D. PIK3CA and ESR1 mutations

2.

Patient Case: A 59-Yr-Old Woman With de Novo MBC

59-yr-old postmenopausal woman was diagnosed with de novo metastatic with ER+/HER2- breast cancer in 2020

At that time, she initiated first-line therapy with a CDK4/6i (palbociclib) + letrozole
- NGS on bone biopsy showed no specific actionable mutations

Disease has been well controlled for the past 5 yr, but the most recent restaging suggests asymptomatic progression in bone

Current NGS by ctDNA shows ESR1 D538G mutation but no PIK3CA/ AKT/PTEN pathway alteration(s)
- No germline BRCA1/2 mutation

At this time, which of the following would you recommend as the best next step for this patient?

A. Abemaciclib + fulvestrant
B. Everolimus + fulvestrant
C. Elacestrant monotherapy
D. Imlunestrant + abemaciclib
E. Trastuzumab deruxtecan monotherapy

3.

In the phase III EMBER-3 trial for patients with ER+/HER2- ABC, which of the following was reported with imlunestrant ± abemaciclib vs SoC ET?

A. Improvement in both PFS and OS with imlunestrant monotherapy vs SoC ET in all patients regardless of ESR1 mutation status
B. Improved PFS only with imlunestrant monotherapy vs SoC ET in all patients regardless of ESR1 mutation status
C. Improved PFS with imlunestrant + abemaciclib vs imlunestrant alone in all patients regardless of ESR1 mutation status
D. Equivalent PFS with imlunestrant + abemaciclib vs imlunestrant alone in patients with previous treatment with a CDK4/6i

4.

Patient Case: A 62-Yr-Old Woman With MBC

62-yr-old postmenopausal woman has achieved stable disease on first-line letrozole plus ribociclib for ER+/HER2- MBC for the past yr

She enrolled in the first step of the phase III SERENA-6 trial, which involves ctDNA surveillance every 2-3 cycles for ESR1 mutation–positive disease

ctDNA analysis reveals the presence of an ESR1 mutation in the absence of clinical progression, and she is randomized to camizestrant + abemaciclib

Now, you are in a morning huddle with your clinical team discussing patient care

At this time, what toxicities specific to camizestrant will you review with your clinical team?

A. Alopecia and hypertension
B. Fatigue and pruritus rash
C. Hearing loss and arthralgia
D. Photopsia and bradycardia
E. QT prolongation and bleeding

5.

What would you tell your patient with progression on 1L CDK4/6i + ET about the rationale for use of an oral SERD or PI3K/AKT pathway inhibitor?

A. Alpelisib and capivasertib inhibit the PI3K pathway in PIK3CA-mutant MBC, but capivasertib is better tolerated with fewer patients requiring discontinuation vs alpelisib
B. ESR1, PIK3CA, and AKT mutations are commonly acquired when HR+/HER2- MBC develops resistance to CDK4/6i plus AI therapy
C. Elacestrant has better efficacy compared with fulvestrant following disease progression on a CDK4/6i regardless of ESR1 mutation status
D. It is important to biopsy MBC tumor tissue after progression on a CDK4/6i to optimize the detection of the presence of an ESR1 mutation or any PI3K/AKT/PTEN pathway alteration

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Overcoming Endocrine Resistance in HR+/HER2- MBC: Tailoring Treatment for Patients With ESR1- and PI3K/AKT/PTEN-Altered Disease Post-ET Progression

Erica L. Mayer, MD, MPH, FASCO

Ruth O'Regan, MD

Joyce O'Shaughnessy, MD

Pretest

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