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About This Activity

Activity Description and Learning Objectives

In this activity, experts in advanced breast cancer discuss the optimization of CDK4/6 inhibitor treatment in patients with advanced breast cancer.  This activity was recorded at the International Consensus Conference for Advanced Breast Cancer 2019 (ABC5) in Lisbon, Portugal, 14–16 November 2019.

This activity has been jointly provided by Oakstone and touchIME ONCOLOGY.  Oakstone Publishing is accredited by the ACCME to provide continuing medical education to physicians.

After watching this activity, participants should be able to:

Target Audience

This activity has been designed to meet the educational needs of breast cancer specialists, general oncologists and other healthcare professionals interested in the treatment of breast cancer, including obstetricians and gynaecologists, and nurse practitioners.

Disclosures

Oakstone Publishing has assessed conflict of interest with its faculty, authors, editors, and any individuals who were in a position to control the content of this CME activity. Any identified relevant conflicts of interest were resolved for fair balance and scientific objectivity of studies utilized in this activity. Oakstone Publishing’s planners, content reviewers, and editorial staff disclose no relevant commercial interests.

Professor Patrick Neven discloses: Advisory role for Eli Lilly, Novartis, Pfizer, Roche (to institution). Research funding/support from Kom op Tegen Kanker (to institution). 

Dr Shaheenah Dawood discloses: Advisory role for AstraZeneca and Roche. Research finding/support from Jalila Foundation and MSD. Lecture fees/Honoraria from AstraZeneca, Biologics, BMS, Lilly, Pfizer, Roche. 

Professor Rupert Bartsch discloses: Advisory role for AstraZeneca, Celgene, Daiichi, Eisai, Eli Lilly, MSD, Novartis, Pfizer, Roche, Samsung. Research funding/support from Daiichi Sankyo, Novartis, Roche. Lecture fees/Honoraria from Accord, AstraZeneca, BMS, Celgene, Eli Lilly, Novartis, Pfizer, Roche, Sandoz.

Content Reviewer

Walter Murray Yarbrough, MD has no financial interests/relationships or affiliations in relation to this activity.

Touch Medical Director

Holly Gilbert-Jones has no financial interests/relationships or affiliations in relation to this activity.

Requirements for Successful Completion

Oakstone Publishing designates this enduring material for a maximum of 1.0 AMA PRA Category 1 Credit™️. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

In order to receive credit for this activity, participants must review and complete the post-test and evaluation form. A score of 70% or higher is needed to obtain CME credit. Statements of credit are awarded upon successful completion of the post-test and evaluation form.

Date of original release: December 5, 2019.  Date credits expire: December 5, 2020.

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Q1. In which subgroups of patients are CDK4/6 inhibitors typically ineffective in combination with first-line endocrine therapy for advanced breast cancer?

  1. a) Patients with visceral metastases
  2. b) Premenopausal patients
  3. c) No subgroups have been identified that are unsuitable for CDK4/6 inhibitor therapy
  4. d) Patients with a short disease interval

Please try again

Subgroup analyses in first-line studies of CDK4/6 inhibitors plus endocrine therapy in advanced breast cancer have shown that all patient subgroups derive a progression-free survival benefit from the addition of a CDK4/6 inhibitor to treatment.

References
Rugo H, et al. Palbociclib plus letrozole as first-line therapy in estrogen receptorpositive/human epidermal growth factor receptor 2-negative advanced breast cancer with extended follow-up. Breast Cancer Res Treat 2019;174:719–729
Hortobagyi GN, et al. Updated results from MONALEESA-2, a phase III trial of first-line ribociclib plus letrozole versus placebo plus letrozole in hormone receptor-positive,
HER2-negative advanced breast cancer Ann Oncol 2018;29:1541–1547
Johnston SJ, et al. MONARCH 3 final PFS: a randomized study of abemaciclib as initial therapy for advanced breast cancer. npj Breast Cancer 2019;5:5
Tripathy D, et al. Ribociclib plus endocrine therapy for premenopausal women with hormone-receptor-positive, advanced breast cancer (MONALEESA-7): a randomised phase 3 trial. Lancet Oncol. 2018;19:904–915

Q2. What are the most common adverse events associated with CDK4/6 inhibitors (all grades)?

  1. a) Nausea with ribociclib and abemaciclib, and neutropenia with palbociclib
  2. b) Leucopenia for all three available DCK4/6 inhibitors
  3. c) Neutropenia with palbociclib and ribociclib, and diarrhoea with abemaciclib
  4. d) Diarrhoea with abemaciclib and palbociclib, and neutropenia with ribociclib

Please try again

The most common any-grade adverse event with palbociclib and ribociclib is neutropenia, and the most common any-grade adverse event with abemaciclib is diarrhoea.

References
Turner NC, et al. Palbociclib in Hormone-Receptor-Positive Advanced Breast Cancer. N Engl J Med. 2015;373:209–19.
Slamon DJ, et al. Phase III Randomized Study of Ribociclib and Fulvestrant in Hormone Receptor–Positive, Human Epidermal Growth Factor Receptor 2–Negative Advanced Breast Cancer: MONALEESA-3. J Clin Oncol 2018;36:2465–2472
Sledge GW Jr, Toi M, Neven P, et al. MONARCH 2: abemaciclib in combination with fulvestrant in women with HR+/HER2- advanced breast cancer who had progressed while receiving endocrine therapy. J Clin Oncol. 2017;35(25):2875-2884.

Q3. Your patient, a postmenopausal woman receiving a CDK4/6 inhibitor + fulvestrant for advanced breast cancer, experiences grade 3 neutropenia soon after starting combination therapy. How should you address her treatment in light of this adverse event?

  1. a) Consider a dose reduction or interruption for the CDK4/6 inhibitor
  2. b) Consider a dose reduction or interruption for endocrine therapy
  3. c) Discontinue fulvestrant
  4. d) Discontinue CDK4/6 inhibitor

Please try again

The 4th ESO-ESMO International Consensus Guidelines for advanced breast cancer state that neutropenia is the most common toxicity associated with CDK4/6 inhibition and is not generally associated with febrile neutropenia, although an increase in infections has been reported. Treatment should be delayed until neutrophils have recovered to at least 1000/μL; dose reduction can also be considered.

Reference
Cardoso F, et al. 4th ESO–ESMO International Consensus Guidelines for Advanced Breast Cancer. Ann Oncol. 2018;29:1634–1657

Q4. How should CDK4/6 inhibitor therapy be adapted for patients who have exhibited primary or secondary resistance to endocrine therapy?

  1. a) Increase dose
  2. b) CDK4/6 inhibitors should only be given as monotherapy
  3. c) CDK4/6 inhibitors should not be given to endocrine-resistant patients
  4. d) Endocrine resistance does not affect dosing or suitable combinations with CDK4/6 inhibitors

Please try again

Clinically meaningful survival benefits have been demonstrated in endocrine-resistant patients for CDK4/6 inhibitors in combination with fulvestrant versus fulvestrant plus placebo.

References
Turner NC, et al. Overall Survival with Palbociclib and Fulvestrant in Advanced Breast Cancer. New Engl J Med 2018;379:1926–1936
Slamon DJ, et al. Overall Survival Results From the Phase III MONALEESA-3 Study of Fulvestrant ± Ribociclib in Postmenopausal Patients With HR+/HER2− Advanced Breast Cancer. Oral presentation at ESMO 2019;abstract LBA_7
Sledge GW, et al. The Effect of Abemaciclib Plus Fulvestrant on Overall Survival in Hormone Receptor–Positive, ERBB2-Negative Breast Cancer That Progressed on Endocrine Therapy—MONARCH 2 A Randomized Clinical Trial. JAMA Oncol 2019; doi:10.1001/jamaoncol.2019.4782

Q5. Which would be the most appropriate next therapy for a postmenopausal women who develops bone metastases during adjuvant tamoxifen for early breast cancer?

  1. a) Cytotoxic chemotherapy
  2. b) CDK4/6 inhibitor + aromatase inhibitor or fulvestrant
  3. c) Everolimus + aromatase inhibitor
  4. d) Fulvestrant monotherapy

Please try again

The 4th ESO-ESMO International Consensus Guidelines for advanced breast cancer state that the addition of a CDK4/6 inhibitor to fulvestrant or an aromatase inhibitor (depending on prior endocrine therapy exposure) is a preferred first-line option.

Reference
Cardoso F, et al. 4th ESO–ESMO International Consensus Guidelines for Advanced Breast Cancer. Ann Oncol. 2018;29:1634–1657

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Learning Objectives Introduction

Introduction

Watch an internationally renowned faculty discuss the optimization of CDK4/6 inhibitor treatment in patients with advanced breast cancer. Prof. Patrick Neven, Dr Shaneenah Dawood and Prof. Rupert Bartsch discuss treatment selection and sequencing, and future directions in the management of HR+/HER2– advanced breast cancer.

The information in this activity is intended for oncologists and other healthcare professionals involved in the treatment of patients with advanced breast cancer.

This ACCME-accredited touchSATELLITE SYMPOSIUM was recorded live during the International Consensus Conference for Advanced Breast Cancer 2019 (ABC5).  The live voting content is no longer active for this symposium.

Learning objectives

After watching this touchSATELLITE SYMPOSIUM, you should be able to:

1 AMA PRA Category 1 CreditsTM. Date of original release: December 05, 2019. Date credits expire: December 05, 2020.

Credit Back to Education Zone

touchSATELLITE SYMPOSIUM

Are we moving towards true optimization of CDK4/6 inhibition in patients with HR+/HER2– advanced breast cancer?

1 AMA PRA Category 1 CreditsTM. Date of original release: December 05, 2019. Date credits expire: December 05, 2020.

Module 2: How different are the adverse event profiles for the CDK4/6 inhibitors and what impact do they have on monitoring and adherence?

Prof. Patrick Neven presents practical considerations for effective adverse event management and monitoring requirements with CDK4/6 inhibitors in HR+/HER2– advanced breast cancer, including a real-world case study.

You have successfully completed: Module 2: How different are the adverse event profiles for the CDK4/6 inhibitors and what impact do they have on monitoring and adherence?

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